Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.5203439
Attempts to were made to assess the interactions of ACTH with the principal binding regions of the ACTH receptor by analysis of binding of radioactive , iodinated ACTH 1 24 . 0.5203439^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.55746891
This is the first report clearly demonstrating that the ACTH receptor binds only ACTH , but not other melanocortin peptides . . 0.55746891^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Associated with this decline in pituitary POMC , levels of the major 3 . 4 kb mRNA transcript for the ACTH receptor expressed as a ratio of beta actin were approximately 80 % lower ( P < 0 . 05 ) in fetal adrenals of betamethasone treated baboons ( 0 . 12 + / 0 . 02 ) than in untreated controls ( 0 . 84 + / 0 . 05 ) . ^^^ These findings indicate that treatment of the baboon fetus with betamethasone in late gestation suppressed fetal pituitary POMC mRNA expression and ACTH receptor mRNA levels in the fetal adrenal gland , as well as the hypertrophy and ACTH receptor mRNA and 3beta HSD mRNA / protein levels in the cells comprising the newly emerging definitive zone . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Total RNA was isolated from the pituitary and adrenal glands to evaluate gene expression for mRNA specific for pro opiomelanocortin ( POMC ) and for the ACTH receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The hypothalamus , pituitary gland , adrenal glands , and liver were immediately obtained to determine the amounts of corticotropin releasing hormone ( CRH ) , beta endorphin , and mRNA for pro opiomelanocorticotropin ( POMC ) , the ACTH receptor ( ACTH R ) , and insulin like growth factor 1 ( IGF 1 ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
There is a progressive and concurrent increase of ACTH 1 39 and cortisol ( F ) in the circulation of fetal sheep during the last 15 20 days of pregnancy ( term , day 145 150 ) associated with increased expression of hypothalamic CRH pituitary POMC and adrenal ACTH receptor and steroidogenic enzymes , particularly P 450 C17 . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The study shows that some parts of the MC system are highly conserved through vertebrate evolution , such as regions in POMC coding for ACTH , alpha MSH , and beta MSH , the C terminal region of AGRP , key binding units within the MC1R , MC2R , MC4R , and MC5R , synteny blocks around the MCRs , pharmacological properties of the MC2R , whereas other parts in the system are either missing , such as the MC3R and gamma MSH , or different as compared to mammals , such as the affinity of ACTH and MSH peptides to MC1R and MC4R and the anatomical expression pattern of the MCRs . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In vivo , activation of the ACTH receptor ( ACTHR ) has a trophic effect on the adrenal cortex , while the effects on proliferation are still under discussion , especially since other POMC derived peptides have been characterized . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Brain , pituitary gland , and adrenal gland were obtained to determine the mRNA levels for corticotropin releasing hormone ( CRH ) , CRH receptor 1 ( CRHR 1 ) , pro opiomelanocortin ( POMC ) , ACTH receptor ( MC2R ) , c jun and c fos . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Adrenal cell suspensions prepared from rats bearing the MtTF 4 tumor failed to increase corticosterone production when exposed to adenosine 3 ' , 5 ' cyclic monophosphate ( cyclic AMP ) or ACTH , placing the defect in these adrenals beyond the ACTH receptor site . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In two cases where the lack of action of ACTH was related to an anomaly of ACTH receptor , the protein kinase activity was normal . ^^^ In the other two cases the ACTH receptor was normal , but the protein kinase activity was different from that of the normal adrenal . ^^^ Therefore , the lack of response to ACTH of some adrenocortical human tumors may be attributed either to an anomaly of the ACTH receptor or to some defect of the cAMP dependent protein kinase . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
These findings further support the hypothesis that fetal ACTH plays a role in the normal development of the adenylate cyclase catalytic portion of the ACTH receptor complex and adrenal differentiation during this critical period of fetal life . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH receptor levels in lamb adrenals at late gestation and early neonatal stages . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In vitro the lack of ACTH ' s action was related to an anomaly of ACTH receptor with normal protein kinase activity . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The administration of single dose of ACTH ( ACTH residues 1 39 ; 200 mU / kg , 4 ) or repeated doses of ACTH R ( ACTH in saline containing 16 % gelatin ; 15 U / kg , sc , twice daily ) reduced the decrease in adrenal DBI LI caused by hypophysectomy . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
These findings suggest that the anti receptor antibody recognizes the ligand binding domain of the ACTH receptor . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Expression of the ACTH receptor in individual stage 5 and 6 oocytes was monitored by radioimmunoassay of ligand stimulated cAMP production . ^^^ Size fractionation of rat adrenal poly ( A ) + RNA by sucrose density gradient centrifugation revealed that mRNA encoding the ACTH receptor was present in the 1 . 1 to 2 . 0 kilobase fraction . ^^^ This system should permit more complete characterization and expression cloning of the ACTH receptor . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
If such lymphocyte binding , as has been suggested , reflects adrenal ACTH receptor activity , these data would suggest that the glucocorticoid deficiency of Allgrove syndrome is not the result of a defect in that receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
This suggests that the defect in autonomous glands is not located at the level of the ACTH receptor , but , rather , involves the adenylate cyclase complex as a whole or its coupling to cAMP dependent protein kinase . ^^^ This points to a defect in the adenoma cells beyond the ACTH receptor . 2 ) Adrenal adenoma formation in patients with Cushing ' s syndrome is accompanied by a relative blockade of 11 beta hydroxylase activity . 3 ) By comparing the preoperative dynamic tests of the pituitary adrenal axis , the plasma ACTH concentration , the morphology of the adrenal glands , and their in vitro responsiveness , a gradual transition from pituitary to ( partial ) adrenal autonomy could be recognized in several patients . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
These findings show that anti HTCA competes with ACTH for binding to the ACTH receptor . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
These results suggest that amphibian adrenocortical cells contain only one class of ACTH receptor which recognizes the 11 24 domain of ACTH with an affinity which depends on the presence of a strong potentiator segment , located at the N terminus end of ACTH ( 1 39 ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Signal transduction in the ACTH receptor : activation by microaggregation . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
However , ACTH receptor expression by these cell populations was not static as suggested by the ability to induce receptor expression via mitogens . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In addition , cortisol modulates the mechanism by which ACTH activates fetal adrenal function , possibly through an action at the level of the ACTH receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Thus , metabolic inhibition permits demonstration of ACTH receptor binding only , unconfounded by sequestration or internalization of ligand : receptor complexes . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The variations in ACTH receptor number were associated with parallel changes on acute ACTH induced cyclic AMP production . ^^^ Thus , the effects of TGF beta on ACTH receptor content are likely another important negative action of this peptide on adrenocortical cell differentiation . ^^^ Moreover , these results suggest that regulation of ACTH receptor number may be one mechanism by which hormones and growth factors control adrenocortical differentiation . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The molecular weight of the ACTH receptor appears to be between 83 and 100 KD . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
This result indicates that the bovine adrenal ACTH receptor , whose identification and characterization have proved difficult , has an Mr of about 40 , 000 . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
An ACTH receptor on human mononuclear leukocytes . ^^^ Relation to adrenal ACTH receptor activity . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
To investigate this possibility , we measured some ACTH receptor parameters in isolated adrenocortical cells from normal and dietary protein restricted domestic fowl . ^^^ Inhibitor constants of hACTH ( 7 38 ) , calculated from Schild plots , were 3 . 16 10 10 ( 7 ) and 9 . 82 10 10 ( 7 ) M for L and N cockerel cells , respectively , thus suggesting differences in ACTH receptor function between the two treatment groups . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
This protein may well represent the long sought , adenylate cyclase linked , low affinity ACTH receptor or a portion thereof . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH receptor mediated induction of leukocyte cyclic AMP . ^^^ Immunofluorescence assays , employing an antiserum to the adrenal cell ACTH receptor , indicated that 45 % of splenocytes , 69 % of S49A cells , and less than 1 % of Molt 4 cells possess ACTH receptors . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
That this binding might result from one peptide being an `` internal image ' ' of the other was strongly suggested by the observation that antibody to the peptide that was encoded by the complementary RNA for ACTH recognized the adrenal cell ACTH receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
However , 9 tryptophan ( O nitrophenylsulfenyl ) ACTH was 8 times more potent with fowl cells than with rat cells , thus suggesting that ACTH receptor differences exist between the two cell types . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
This effect supports the hypothesis of a direct interaction between lipopolysaccharide and the cell membrane with a concomitant distortion of the cell surface affecting the ACTH receptor sites of their environment . [ 14C ] Lipopolysaccharide binds to isolated adrenocortical cells . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Behavioral support for an ACTH receptor in the CNS . ^^^ In this report we present a series of experiments which have led us to support the notion of the presence of an ACTH receptor in the CNS . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Using immunoaffinity chromatography the ACTH receptor was purified , and the molecular structure and 125I ACTH binding characteristics were determined . ^^^ A molecular weight ( Mr ) of 225 000 was determined for the complete ACTH receptor as analyzed by sodium dodecyl sulfate ( SDS ) polyacrylamide gel electrophoresis . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The inhibitory action of vanadium compounds was also seen when cholera toxin or forskolin was used as a stimulant instead of ACTH , indicating that vanadate does not act on the ACTH receptor protein . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Our attempts to develop adrenocorticotropic hormone ( ACTH ) analogues that can be employed for ACTH receptor identification and isolation began with the synthesis of ACTH fragments containing N epsilon ( dethiobiotinyl ) lysine ( dethiobiocytin ) amide in position 25 to be used for affinity chromatographic purification of hormone receptor complexes on Sepharose immobilized avidin resins . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Characterization of the porcine ACTH receptor with the aid of a monoclonal antibody . ^^^ Monoclonal antibodies were raised against the ACTH receptor by immunization of BALB 1 c mice with porcine adrenal cortex cell membranes . ^^^ Competition and binding experiments confirmed that one of these antibodies , IV / 14 / 9 , reacted with the ACTH receptor in competition with ACTH and caused a definite ACTH like effect . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Comparison of the activity profile of additional compounds , such as des acetyl alpha MSH , ( Tyr ( 1 ) 2 ) alpha MSH , ( Trp ( For ) 9 ) alpha MSH or ( Nva 12 ) alpha MSH , in the adrenocortical and pigment cell assays led to the conclusion that alpha MSH does not exert its steroidogenic effect through a typical melanocyte type of MSH receptor , but rather through a low affinity type of ACTH receptor . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The present investigation was performed in order to study the properties of abnormal membrane function related to ACTH receptor adenylate cyclase system interaction in human ACTH unresponsive adrenocortical cancer . ^^^ These results suggest that the lack of ACTH receptor at the cell membrane surface might be responsible for ACTH unresponsiveness in the CS tissue , although an accelerated degradation of GTP could contribute to decreased activity of GTP binding protein . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Neuraminidase appeared to alter a carbohydrate containing ACTH receptor preventing ACTH binding . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
It is suggested that ACTH ganglioside interactions will participate in ACTH receptor interactions . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Ontogeny of the ACTH receptor , adenylate cyclase and steroidogenesis in adrenal . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
A specific and sensitive assay for determining the binding of adrenocorticotropin ( ACTH ) to isolated rat adipocytes has been developed and utilized to study the effect of glucocorticoids on ACTH receptor . ^^^ Our results indicate that glucocorticoids do not cause their permissive effects by specific regulation of the ACTH receptor on the adipocyte . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The data on mouse adipocyte membrane suggests that the coupling of ACTH receptor to adenylate cyclase is dependent on GTP and that catecholamine activation of adenylate cyclase is less dependent on this nucleotide . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
These results together with previous data showing that the magnitude and time course of the adrenal cAMP response to ACTH changes diurnally strongly suggest that ACTH receptor affinity or coupling with adenylate cyclase changes diurnally . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
It is suggested that p 68 may regulate the transfer of information from the occupied ACTH receptor ot the catalytic subunit of adenylate cyclase . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Existence of a specific ACTH receptor was demonstrated using 125I radioiodinated ACTH 1 24 . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The data suggest that alpha MSH at low concentrations ( less than 10 ( 7 ) mol / l ) interacts with a glomerulosa cell receptor which is distinct from the ACTH receptor but interacts with the ACTH receptor at concentrations greater than 10 ( ' 5 ) mol / l . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Both the specificity and lack of specificity of the action of this agent to influence the activity of the 3 secretagogues suggest that naloxone and possibly a naturally occurring endogenous ligand interacts with one or more membrane receptor distinct from the ACTH receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The steroid specificity of suppression of cyclic AMP ( cAMP ) induced and ACTH induced steroidogenesis were similar , suggesting that suppression is not solely the result of interference with ACTH receptor function or the induction of adenylate cyclase activity . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The effects of ions on the level of ACTH receptor mRNA were also analyzed . ^^^ ACTH receptor mRNA levels remain unaffected by either low sodium or high potassium intake . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH receptor deficient mutants of the Y 1 mouse adrenocortical tumor cell line . ^^^ As determined from Northern blot and RNase protection assays , ACTH resistance in these mutants results from the failure to accumulate ACTH receptor transcripts . ^^^ The ACTH receptor gene appears to be present in these mutants as determined by Southern blot hybridization analysis and can be activated following the growth of the mutant cells as tumors in mice , suggesting that the ACTH receptor gene is modified in a reversible manner . ^^^ These results suggest that the adenylyl cyclase system in the mutants is otherwise intact and that the failure to express ACTH receptor transcripts limits the responsiveness of these clones to the hormone . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In the present work , we have studied the effects of both hormones on ACTH receptor ( ACTH R ) mRNA and binding sites . ^^^ Both HAC and BAC expressed several ACTH R transcripts . ^^^ Although in both cell types , ACTH and A 2 increased ACTH R transcripts in a time and dose dependent manner , the maximal effects were different . ^^^ Thus , ACTH at 10 ( 9 ) M enhanced 21 and 5 fold the level of ACTH R mRNA and binding sites in HAC , whereas in BAC both parameters were enhanced only 3 fold . ^^^ A 2 at 10 ( 7 ) M increased 17 and 3 . 5 fold ACTH R mRNA and binding sites in HAC , whereas in BAC , it caused only a 2 fold increase in ACTH R mRNA and a small decrease in receptor number . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The reason for this defect in ACTH binding remains unclear because no significant mutation in the ACTH receptor DNA sequence was detected in the MNLs of these patients . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
One day later , pigs were killed and adrenal glands obtained for ACTH receptor measurements . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The cloning of the melanocyte stimulating hormone ( MSH ) and adrenocorticotropic hormone ( ACTH ) receptors ( MC 1 R and MC 2 R , respectively ) recently has led to the identification of three additional melanocortin receptors , MC 3 R , MC 4 R , and MC 5 R . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The objective of this study was to investigate the presence of activating mutations of the ACTH receptor gene in benign and malignant adrenocortical tumours . ^^^ Genomic DNA was extracted from a variety of adrenocortical neoplasms from 16 patients and the entire ACTH receptor gene was then amplified by the polymerase chain reaction and sequenced . ^^^ No mutations were detected within the coding region of the ACTH receptor gene in the 16 adrenocortical tumours studied . ^^^ It is likely that mutations of the coding region of the ACTH receptor gene do not play a major role in adrenocortical tumourigenesis . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Pathogenetic mutations have been identified in the ACTH receptor gene in families with isolated familial ACTH unresponsiveness . ^^^ Whether the ACTH receptor represents the locus of the defect for the triple A syndrome is not known . ^^^ Screening for abnormalities of the ACTH receptor gene by single strand conformation polymorphism analysis revealed no abnormality . ^^^ Direct sequencing of the entire coding area of the ACTH receptor gene was also normal . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
A novel mutation of the adrenocorticotropin receptor ( ACTH R ) gene in a family with the syndrome of isolated glucocorticoid deficiency , but no ACTH R abnormalities in two families with the triple A syndrome . ^^^ Mutations in the ACTH receptor gene have been reported in several families with IGD . ^^^ We have amplified and directly sequenced the entire intronless ACTH receptor gene in 1 other family with IGD and 2 families with triple A syndrome . ^^^ No mutations were identified in the entire coding area of the ACTH receptor in the 2 families with triple A syndrome , supporting the idea of a developmental or postreceptor defect in this syndrome . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
A polymerase chain reaction generated mouse ACTH R probe was used to screen a mouse genomic library , and a clone of 13kb containing the entire coding sequence was isolated . ^^^ The coding sequence shows 84 % homology with the human gene at the DNA level and encodes a peptide with 89 % homology to the human ACTH R . ^^^ Cloning , characterization and expression of a functional mouse ACTH receptor . ^^^ In conclusion we have cloned a mouse ACTH receptor gene and demonstrated for the first time its expression and functional effect in HeLa cells . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Characterization of the transcription start site of the ACTH receptor gene : presence of an intronic sequence in the 5 ' flanking region . ^^^ Analysis of the ACTH receptor mRNA in human adrenal has revealed the presence of five transcripts ranging from 1 . 8 to 11 kilobases ( kb ) . ^^^ Characterization of the 5 ' untranslated regions ( UTRs ) of the ACTH receptor mRNA demonstrated the presence of one major initiation site of transcription 177 bp away from the ATG codon . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The ACTH receptor mRNA and the MSH receptor mRNA were expressed only in the adrenal and melanocytes , respectively . ^^^ For analysis of the transcriptional regulation of ACTH receptor in Y 1 cells , 1 have isolated the mouse ACTH receptor gene . ^^^ A 914 bp DNA fragment of the human ACTH receptor gene was amplified by polymerase chain reaction and used as a probe . ^^^ By comparing it with the previously reported human ACTH receptor gene and bovine ACTH receptor cDNA , the mouse homologue is intron less in its coding region , and has a potential to encode for a 296 amino acid polypeptide which possesses 88 . 9 % and 78 . 7 % identities to the human and bovine ACTH receptors , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
These results suggest that renin independent overproduction and clinically observed ACTH dependent production of aldosterone in APAs may results from the enhanced transcription of P450c11 and ACTH receptor genes . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Defects of the ACTH receptor have been suggested as a possible cause , and we have previously reported a number of novel mutations of the ACTH receptor gene in some , but not all , cases , suggesting that familial glucocorticoid deficiency may have a heterogeneous molecular etiology . ^^^ Here we report the clinical features and ACTH receptor gene analysis in four patients from different families . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The complementary peptide approach has also been used to produce antibodies specific for the ACTH receptor complex . ^^^ Monospecific antibodies to the ACTH ( 1 24 ) complementary peptide caused an ACTH like steroidogenic response of cultured mouse adrenal cells , presumably by binding to the ACTH receptor , and binding was specifically inhibited by ACTH . ^^^ The ACTH receptor complex from solubilized adrenal cells was shown to consist of four subunits with M ( r ) 83 , 000 , 64 , 000 , 52 , 000 , and 22 , 000 . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
To examine whether the ACTH receptor ( ACTH R ) gene could be an oncogene in human adrenocortical tumors , we amplified by the polymerase chain reaction and directly sequenced the entire exon of the ACTH R gene in 25 adrenocortical tumors ( 17 adenomas and 8 carcinomas ) and 2 adrenocortical cancer cell lines . ^^^ We conclude that activating mutations of the ACTH R gene do not represent a frequent mechanism of human adrenocortical tumorigenesis . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Using cultured human fetal adrenal cells , we have investigated the basal secretion of cortisol and dehydroepiandrosterone sulfate ( DHAS ) and the effect of corticotropin ( ACTH ) , angiotensin 2 ( A 2 ) and transforming growth factor beta 1 ( TGF beta 1 ) on the secretion of these steroids and on the mRNA levels of ACTH receptor ( ACTHR ) , cytochrome P 450scc ( cholesterol side chain cleavage ) , P 450 17 alpha ( 17 alpha hydroxylase / 17 20 lyase ) and 3 beta HSD ( 3 beta hydroxysteroid dehydrogenase ) . ^^^ A 2 treatment also increased the secretion of both DHAS and cortisol , but less than ACTH , enhanced the responsiveness to ACTH and increased ACTHR , P450scc and P 450 17 alpha mRNA levels . ^^^ Moreover , TGF beta 1 had no effect on ACTHR and P450scc mRNA levels , decreased by about 50 % the mRNA levels of P 450 17 alpha both in the absence or presence of ACTH , but enhanced the stimulatory effects of ACTH on 3 beta HSD mRNA . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We now demonstrate that ACTH resistance in the Y 6 and OS 3 mutants results from the failure to express the gene encoding the ACTH receptor . ^^^ Whereas parental Y 1 cells express ACTH receptor transcripts at low levels and are stimulated by ACTH or 8 bromo cAMP to increase the accumulation of ACTH receptor transcripts approximately twofold , the Y 6 and OS 3 mutants do not express receptor transcripts either in the presence or absence of 8 bromo cAMP . ^^^ The gene encoding the ACTH receptor appears to be present in the Y 6 and OS 3 mutants , as determined by Southern blot hybridization analysis . ^^^ Moreover , in the Y 6 mutant the ACTH receptor gene appears to be silenced by a modification that is reversed following the growth of the cells as tumors in mice . ^^^ Clonal isolates of Y 6 cells grown as tumors recover the ability to express ACTH receptor transcripts at low but detectable levels and acquire the ability to respond to ACTH with increased adenylyl cyclase activity . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The melanocortin receptor family includes the melanocyte stimulating hormone receptor ( MSH R ) , adrenocorticotropic hormone receptor ( ACTH R ) , and two neural receptors , MC 3 R and MC 4 R . ^^^ In the human these receptors map to 16q24 ( MSH R ) , 18p11 . 2 ( ACTH R ) , 20q13 . 2 ( MC 3 R ) , and 18q22 ( MC 4 R ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Bovine adrenal fasciculata reticularis cells ( BAC ) expressed at least four ACTH receptor ( ACTH R ) mRNA transcripts , one major of 3 . 6 kb and three minor of 4 . 2 , 1 . 8 and 1 . 3 kb . ^^^ ACTH and A 2 increased ACTH R mRNA levels in a time and dose dependent manner . ^^^ The results indicate that regulation of ACTH R mRNA levels may be one mechanism by which ACTH and A 2 regulate adrenocortical functions . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
TGF beta 1 alone had no effect on ACTH receptor messenger ribonucleic acid ( mRNA ) levels and was unable to reduce the strong stimulatory effects of ACTH on its own receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Mutations of the ACTH receptor gene are only one cause of familial glucocorticoid deficiency . ^^^ Defects in the ACTH receptor have been suggested as a possible cause , and we have previously reported a point mutation in this gene in a family with FGD . ^^^ Investigation of seven additional families has revealed a number of novel mutations in the ACTH receptor in some , but a normal gene in others suggesting that the aetiology of FGD may be heterogeneous . ^^^ Using a highly polymorphic CA repeat marker ( D18S40 ) closely linked to the ACTH receptor locus , we are now able to confirm that some cases of FGD result from defects at another locus . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We investigated the DNA base sequence in a family with this condition by polymerase chain reaction amplification of DNA with pairs of primers that span the ACTH receptor domain . ^^^ The affected male proband showed a single base mutation , ser 74 > ile , in the sequence coding for the second transmembrane domain of the ACTH receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Only one class of ACTH receptor was detected , with Kd = 2 . 57 + / 0 . 35 10 10 ( 9 ) M and Bmax = 1 . 59 + / 0 . 06 pmol / mg protein in high responders and Kd = 1 . 68 + / 0 . 18 10 10 ( 9 ) M and Bmax = 1 . 17 + / 0 . 11 pmol / mg protein in low responders . 4 . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The regulation of ACTH receptor binding sites and mRNA by ACTH and angiotensin 2 ( A 2 ) was studied using cultured human adrenal fasciculata reticularis cells ( HAC ) . ^^^ These cells expressed two major ACTH receptor transcripts of 1 . 8 and 3 . 4 kb and three minor ones of 4 , 7 , and 11 kb . ^^^ At a maximal concentration of 10 ( 8 ) M , ACTH enhanced 21 and 4 fold the level of ACTH receptor mRNA and the number of receptors per cell , respectively . ^^^ Pretreatment of HAC with A 2 produced a dose dependent enhancement of ACTH receptor mRNA that was associated with an increase of both ACTH receptor number and responsiveness to this hormone . ^^^ The effects of ACTH together with A 2 on ACTH receptor mRNA were greater than those induced by each hormone alone . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The maximal stimulatory effect ( 60 70 % rise ) was obtained with a VIP concentration of 10 ( 8 ) M . [ 4 Cl D Phe 6 , Leu 17 ] VIP , a VIP receptor antagonist ( VIP A ) , and corticotropin inhibiting peptide ( CIP ) , an ACTH receptor antagonist ( both 10 ( 6 ) M ) , completely annulled VIP ( 10 ( 8 ) M ) evoked rises in basal ALDO and corticosterone secretions . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We therefore studied the levels of ACTH R mRNA in mouse Y 1 and human NCI H 295 ( H 295 ) adrenocortical carcinoma cell lines . ^^^ ACTH induced an increase in mouse ACTH R mRNA in Y 1 cells that was time and dose dependent , increasing 6 fold over basal levels following exposure to 10 ( 8 ) M ACTH for 19 24 h . ^^^ The amount of human ACTH R mRNA in H 295 cells increased 2 4 fold following a 24 h exposure to 10 ( 8 ) M ACTH , 1 mM dbcAMP , or 10 ( 5 ) M Forskolin . ^^^ Treatment of H 295 cells with angiotensin 2 ( A 2 ) was found to dramatically increase the level of ACTH R mRNA . ^^^ These data indicate that regulation of ACTH R mRNA levels is at least one mechanism by which ACTH and A 2 elevate the number of ACTH binding sites in the adrenocortical cells . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The cDNA and gene of the human ACTH receptor were recently cloned . ^^^ We hypothesized that the ACTH receptor gene might be defective in IGD . ^^^ We conclude that IGD in this family appears to be due to defects of the ACTH receptor gene . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Functional characterization of the cloned human ACTH receptor : impaired responsiveness of a mutant receptor in familial glucocorticoid deficiency . ^^^ The putative ACTH receptor gene has been identified on the basis of its tissue specific expression , structure , and limited expression data . ^^^ The S74I mutant ACTH receptor gene that associates with the syndrome of familial glucocorticoid deficiency had an EC 50 of 67 10 10 ( 9 ) M . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Five Japanese patients with ACTH unresponsiveness were examined as to whether they have mutations in the putative ACTH receptor . ^^^ The coding region of the ACTH receptor gene was amplified by polymerase chain reaction and directly sequenced on both strands , however , no point mutation was found in any of the five patients , suggesting that familial glucocorticoid deficiency , caused by the mutated ACTH receptor , may be rare . . ^^^ Among these MC Rs , MC 2 R is considered to be an adrenocorticotropin ( ACTH ) receptor because its expression is almost localized in the adrenal cortex . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We isolated five independent cDNAs of nearly 3000 bp for the bovine ACTH receptor by screening adrenal cortex cDNA libraries with a PCR cloned cDNA fragment . ^^^ The deduced receptor sequence includes 297 residues ( M ( r ) = 33 , 258 ) with 81 % identity with the human ACTH receptor , and shows seven hydrophobic transmembrane domains . ^^^ Thus , the involvement of protein kinase A and C pathways in ACTH action may be mediated in part by phosphorylation of the ACTH receptor at these motifs . ^^^ The 3 ' untranslated region of the bovine cDNA is > 2000 bp and includes two inverse repeats giving an extensive and strong secondary structure to the ACTH receptor RNA . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Responsiveness of adrenal cortical cells to ACTH is dependent on the extent of ACTH receptor expression . ^^^ Therefore , we examined the localization and regulation of ACTH receptor expression in the midgestation ( 16 24 weeks ) human fetal adrenal cortex . ^^^ In situ hybridization analysis was used to localize messenger RNA ( mRNA ) encoding the ACTH receptor in sections of human fetal adrenal glands . ^^^ Messenger RNA encoding the ACTH receptor was localized in cells from all cortical zones ; abundance was higher in definitive zone than in fetal zone cells and was least abundant in the more central portions of the cortex . ^^^ Regulation of ACTH receptor expression was studied using Northern blot analysis of total RNA extracted from primary cultures of fetal and definitive zone cells . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Northern blot analysis revealed two ACTH R mRNA species with 4 . 0 kb and 2 . 0 kb . ^^^ ACTH R mRNAs in the adenoma tissues were much more abundant than those in the normal tissues from the two patients , suggesting that the mRNA in normal adrenal tissue is either suppressed by cortisol excess or the absence of ACTH . ^^^ To examine the mechanism involved in ACTH R mRNA regulation , the changes in the receptor mRNA caused by ACTH were studied in dexamethasone treated rats . ^^^ Administration of dexamethasone for 5 days resulted in a marked decrease in ACTH R mRNA to an undetectable level . ^^^ A bolus administration of ACTH 1 24 intravenously or ACTH Z 1 24 intramuscularly to the dexamethasone treated rat did not cause any significant change in ACTH R mRNA from 0 . 5 to 12 h after the administration . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
When BAC were incubated with [ 125I ] ACTH in the presence of 100 microM phenylarsine oxide at 20 degrees C , a condition which prevents the internalization of the ACTH receptor complex , the bulk of the radioactivity was present in the 43 , 000 band . ^^^ These results indicate that the ACTH receptor present at the cell surface is a macromolecule of 43 , 000 , and suggest that the 154 , 000 form probably represents association of the ACTH receptor complex to another macromolecule . ^^^ The 154 , 000 protein would be formed during or after internalization of the ACTH receptor complex . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Our results suggest that Addison ' s disease is not caused by circulating antibodies to the ACTH receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Prolonged administration of ACTH R ( ACTH in saline containing 16 % gelatin , 15 U / kg / day , from day 7 after surgery ) to hypophysectomized rats , completely restored DBI and MDR adrenal expression to values similar to those of sham operated rats . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In addition to their antimicrobial and cytotoxic properties , some defensins act as opsonins , while others inhibit protein kinase C , bind specifically to the ACTH receptor and block steroidogenesis or act as selective chemoattractants for monocytes . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The defects in the ACTH receptor causing IGD help illuminate the mechanisms of ligand binding and signal transduction by this receptor . ^^^ Identification of the molecular defect ( s ) responsible for IGD cases with a normal ACTH receptor structural gene and for the triple A syndrome remains a challenge , which will hopefully eventually provide further insight into the mechanisms of adrenocortical function . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The MC 2 receptor exhibits properties similar to the ACTH receptor characterized in adrenocortical cells , coupling to activation of adenylyl cyclase with an EC 50 of approximately 1 nM . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Therefore , in the present study we determined the levels of ACTH receptor messenger RNA ( mRNA ) and correlated ACTH receptor expression with appearance of the mRNA for delta 5 3beta hydroxysteroid dehydrogenase / isomerase ( 3betaHSD ) , the enzyme protein that signals functional maturation of the definitive cortical zone in the baboon fetal adrenal . ^^^ A baboon ACTH receptor complementary DNA was cloned and hybridized with polyadenylated RNA isolated from baboon ( Papio anubis ) fetal adrenals obtained in early ( days 58 64 ; RNA from seven baboon fetuses pooled to yield three samples ) , mid ( days 99 103 ; RNA from five baboons pooled to yield four samples ) , and late ( days 165 168 ; RNA of four individual baboon fetuses ) gestation ( term = 184 days ) . ^^^ Expression of the primary 3 . 4 kilobase ACTH receptor mRNA transcript , determined by Northern blot and expressed as a ratio of beta actin mRNA , was minimal early in gestation ( mean + / SE , 0 . 11 + / 0 . 05 arbitrary densitometric units ) . ^^^ However , fetal adrenal ACTH receptor mRNA levels increased ( P < 0 . 001 , by ANOVA ) approximately 13 fold to 1 . 41 + / 0 . 16 at midgestation , then declined by 70 % ( P < 0 . 001 ) to 0 . 41 + / 0 . 10 in late gestation . ^^^ To determine whether the decrease in ACTH receptor expression by the fetal adrenal in the second half of pregnancy reflected programmed cell death , the integrity of genomic DNA was assessed by 32P labeled DNA gel electrophoresis and in situ DNA end labeling . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Recent cloning of the human ACTH receptor gene has enabled us to study this gene in patients with glucocorticoid deficiency . ^^^ By using the PCR to amplify the coding sequence of the ACTH receptor gene , we identified three mutations in two unrelated patients . ^^^ Normal and mutant ACTH receptor genes were expressed in the M 3 cell line , and intracellular cAMP production in response to ACTH was measured . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH receptor , CYP11A1 , CYP 17 and CYP21A2 genes are expressed in skin . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH and IGF 1 increased c fos and jun B mRNA levels early with later increases in the levels of mRNA for the ACTH receptor and the three steroidogenic enzymes , and enhanced steroidogenic responses to both ACTH and Ang 2 . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The ACTH R is a receptor that has a prominent role in mammalian physiology , but which has been notoriously difficulty to study . ^^^ The ACTH receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Localization of ACTH receptor mRNA by in situ hybridization in mouse adrenal gland . ^^^ This action is presumed to be mediated by the ACTH receptor and is functionally connected with the hypothalamus pituitary adrenal axis . ^^^ To gain information concerning the distribution of the ACTH receptor in this axis , we examined mRNA for the ACTH receptor in the adrenal gland , pituitary and hypothalamus of the mouse , by using in situ hybridization . ^^^ The specific hybridization signal for ACTH receptor mRNA was uniformly distributed in the Y 1 cells , although the level of expression was low . ^^^ The adrenal cortex showed a strong signal for the ACTH receptor mRNA in both the zona fasciculata and the zona glomerulosa , sites that are involved in the mediation of the action of ACTH on the synthesis and release of glucocorticoids and aldosterone . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Germline loss of function mutations in rhodopsin , cone opsins , the V 2 vasopressin receptor , ACTH receptor , and calcium sensing receptor are responsible for retinitis pigmentosa , color blindness , nephrogenic diabetes insipidus , familial ACTH resistance , and familial hypocalciuric hypercalcemia , respectively . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In the present study , we investigated whether the constitutive and ACTH induced expression of ACTH receptor ( ACTH R ) mRNA in bovine adrenocortical cells ( BAC ) requires new protein synthesis . ^^^ The results show that cycloheximide alone , an inhibitor of protein synthesis , induced a time and dose dependent increase in the constitutive level of the ACTH R major transcript of 3 . 6 kb in BAC . ^^^ The effect of cycloheximide involved an increase in the half life and the transcription rate of the major transcript of ACTH R ( 2 and 8 . 4 fold respectively ) . ^^^ In addition , the results also demonstrated that neither the constitutive nor the ACTH induced expression of ACTH R require new protein synthesis . . ^^^ Cycloheximide enhances ACTH receptor mRNA through transcriptional and post transcriptional mechanisms in bovine adrenocortical cells . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The results suggest that beta lipotropin stimulates steroidogenesis by acting on the conversion of cholesterol to pregnenolone and that its effects are not mediated via an opioid receptor but may be mediated via an ACTH receptor . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The cloned mouse ACTH receptor was expressed in stably transfected human HeLa cells that lack an endogenous melanocortin receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Mutations of ACTH receptor gene and familial syndrome of glucocorticoid deficiency ] . ^^^ Recent cloning of the ACTH receptor allowed to study this receptor in this particular syndrome . ^^^ The mutant receptors were expressed in vitro in transfected M 3 cells ( S 91 Cloudman cells ) which represents a working expression system to express the ACTH receptor . ^^^ The EC 50 values were estimated ( C251F : 3 . 5 + / 0 . 9 10 10 ( 9 ) M , D107N : 3 . 0 + / 0 . 9 10 10 ( 9 ) M , G217fs : 4 . 8 + / 0 . 9 10 10 ( 9 ) M ) and comparison with the value obtained for the wild type ACTH receptor ( 5 . 1 + / 0 . 9 10 10 ( 10 ) M ) indicates a clear 6 to 9 shift to the right due to an impaired function of these mutant receptors . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In cells treated with IGF 1 or 2 , the messenger ribonucleic acid ( mRNA ) levels of cytochrome P 450 17 alpha hydroxylase and of 3 beta hydroxysteroid dehydrogenase were increased , and the abundance of ACTH receptor mRNA was also slightly enhanced , but the mRNA of cytochrome P 450 cholesterol side chain cleavage enzyme was unchanged . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
As a step for analysis of the transcriptional regulation of the adrenocorticotropin ( ACTH ) receptor gene , 1 have made an attempt to obtain a full length cDNA and determined the genomic organization of the mouse ACTH receptor . ^^^ By comparison of the 374bp sequence with the 1 . 8kb genomic sequence within the phage clone , lambda mCTR 8 , containing the mouse ACTH receptor coding region as described previously , a 95bp sequence of the 5 ' RACE generated cDNA was found to locate from the position of 1 to 95 from the ATG , and a 113bp sequence of the 5 ' RACE generated cDNA was found in the genomic sequence approximately 1 . 6kb upstream of the ATG . ^^^ The 3 ' non coding region of the mouse ACTH receptor cDNA obtained by 3 ' RACE method was contiguous to the coding region by comparing it with the 1 . 4kb genomic sequence downstream of the ATG . ^^^ Taken together , the mouse ACTH receptor gene consists of at least 4 exons and three of the exons encoded 5 ' untranslated sequences . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We demonstrate that the resistance of these mutants to ACTH results from the failure to express ACTH receptor transcripts . ^^^ Two spontaneous Y 1 mutants , Y 6 and OS 3 , previously characterized as ACTH resistant clones that failed to accumulate ACTH receptor transcripts , were shown to be forskolin resistant and to contain less Gs alpha in membrane fractions , indicating that forskolin resistance , failure to express the ACTH receptor , and the consequent reduction in Gs alpha are closely linked . ^^^ Expression of the human ACTH receptor in Y 6 and OS 3 cells restored ACTH responsive adenylyl cyclase activity and increased the level of Gs alpha , but did not otherwise reverse the forskolin resistant phenotype . ^^^ Together , these results demonstrate that mutations to forskolin resistance have downstream consequences that result in the loss of ACTH receptor expression and the consequent reduction in levels of membrane associated G alpha subunits . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Expression of the mouse ACTH receptor gene and characterisation of its promoter . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Characterization of the human ACTH receptor gene and in vitro expression . ^^^ The coding sequence of the human ACTH receptor , cloned in 1992 , contains no intron , but the presence of one intron ( of about 18 kb ) separating the coding exon from an upstream exon has been demonstrated . ^^^ To functionally characterize the human ACTH receptor , we have prepared cells stably transfected with either the normal receptor or a mutant receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
This study shows that chronic stress leads to a ) inhibition of mineralocorticoid secretion due to inhibition of the late biosynthetic pathway , and b ) increased circulating glucocorticoids due to increased ACTH receptor activity , expression and activity of the early pathway , and decreased glucocorticoid clearance . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Genomic structure and promoter characterization of the human ACTH receptor gene . ^^^ One kb of the 5 ' flanking region of the human ACTH receptor gene was isolated and partially characterized . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We have proposed , therefore , that there is a selective decrease in ACTH receptor expression and thus tropic responsivity to ACTH within the fetal zone in the second half of primate pregnancy . ^^^ ACTH receptor messenger RNA ( mRNA ) levels , determined by in situ hybridization , in the fetal zone of the baboon fetal adrenal were approximately 2 fold greater ( P < 0 . 05 ) at mid ( i . e . day 100 ) than at late ( i . e . day 170 ) gestation and 3 fold greater ( P < 0 . 01 ) in the definitive zone than in the fetal zone in late gestation ( term = 184 days ) . ^^^ Both ACTH receptor and low density lipoprotein receptor mRNA levels , determined by Northern blot in the whole fetal adrenal , also decreased ( P < 0 . 001 ) by approximately 50 % , whereas the mRNA levels for the definitive zone specific delta 5 3beta hydroxysteroid dehydrogenase / isomerase ( 3beta HSD ) enzyme required for cortisol biosynthesis increased over 13 fold ( P < 0 . 001 ) between mid and late gestation . ^^^ We conclude that the decrease in ACTH receptor mRNA expression and ACTH stimulable dehydroepiandrosterone formation in the second half of gestation reflect a decline in functional capacity of the fetal zone , whereas the increase in 3beta HSD mRNA expression and cortisol production results from the ACTH receptor mediated development and enhanced functional capacity of the definitive zone . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We examined the effects of recombinant human IGF 2 and the closely related peptide , IGF 1 , on 1 ) basal and agonist stimulated [ ACTH ( 1 24 ) , forskolin , or 8 bromo cAMP ] cortisol and DHEA S production , 2 ) basal and ACTH stimulated steady state abundance of messenger ribonucleic acids ( mRNAs ) encoding the steroidogenic enzymes cytochrome P 450 side chain cleavage ( P450scc ) and cytochrome P 450 17alpha hydroxylase / 17 , 20 lyase ( P450c17 ) , and 3 ) basal and ACTH stimulated steady state abundance of mRNA encoding the ACTH receptor . ^^^ Neither IGF 1 nor IGF 2 affected basal or ACTH stimulated abundance of mRNA encoding the ACTH receptor , suggesting that the increase in ACTH responsiveness was not mediated by an increase in ACTH binding capacity . ^^^ Taken together , these data indicate that activation of the type 1 IGF receptor increases ACTH responsiveness in fetal zone cells by modulating ACTH signal transduction at some point distal to ACTH receptor activation . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The ACTH receptor is the shortest G protein coupled receptor to date and consists of 297 residues with two putative glycosylation sites at the extracellular N terminus . ^^^ In vitro studies have demonstrated upregulation of the ACTH receptor by its own ligand and by angiotensin 2 . ^^^ Inactivating mutations of the ACTH receptor lead to the familial glucocorticoid deficiency ( FGD ) syndrome , a rare recessive autosomal disorder characterized by degeneration of the zona fasciculata / reticularis and unresponsiveness to exogenous ACTH . ^^^ Interestingly , ACTH receptor mutations are not present in all patients with FGD and also not in the closely related `` triple A ' syndrome indicating that other mechanisms of ACTH resistance are still to be elucidated . ^^^ Despite an extensive search , no activating ACTH receptor mutations have been found in adrenal tumors , excluding the ACTH receptor as a relevant oncogene for adrenal tumorigenesis . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH receptor ] . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Stable expression of normal and mutant human ACTH receptor : study of ACTH binding and coupling to adenylate cyclase . ^^^ Point mutations of the human ACTH receptor have been reported in some patients with a familial glucocorticoid deficiency syndrome . ^^^ We have developed a stable expression model in order to characterize the human ACTH receptor by binding studies and functional coupling to adenylate cyclase . ^^^ The EC 50 for ACTH were 2 . 9 + / 0 . 2 10 10 ( 10 ) M and 2 . 4 + / 0 . 8 10 10 ( 10 ) M , respectively , for two different clones stably expressing the normal human ACTH receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We propose that the most likely molecular mechanism for the multiple ACTH R mRNA transcripts is the alternative use of polyadenylation signals . . ^^^ We present 2 . 59 kb of the 3 ' non coding region of the ACTH receptor cDNA that contains seven potential polyadenylation signals . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In 6 , mutations , in the coding region of the ACTH receptor are the cause of their ACTH resistance . ^^^ MEASUREMENTS : Physical examination , basal serum cortisol , basal plasma ACTH , serum cortisol after stimulation with 250 micrograms ACTH ( 1 24 ) , plasma dehydroepiandrosterone sulphate ( DHEAS ) and plasma androstenedione ( A 4 ) , total urinary androgen excretion and single stranded sequencing of the coding region of the ACTH receptor . ^^^ The lack of adrenarche was independent of the presence of a mutation within the ACTH receptor and of the severity of glucocorticoid deficiency . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Among these , the adrenal ACTH receptor ( MC 2 R ) is selectively activated by ACTH . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The ACTH receptor ( ACTH R ) has recently been cloned , allowing systematic evaluation of its expression and function in adrenal tumorigenesis . ^^^ We investigated ACTH R and P 450 side chain cleavage enzyme ( P450scc ) mRNA expression in a variety of neoplastic adrenocortical tissues by Northern blot and reverse transcriptase PCR ( RT PCR ) . ^^^ Poly A mRNA was electrophoresed , immobilized on a nylon membrane and hybridized using alpha 32P CTP labelled human ACTH R and P450scc cDNAs . ^^^ RESULTS : Mean ACTH R mRNA expression showed significant differences between groups ( P = 0 . 0001 ) , but appeared to be independent of plasma ACTH concentrations . ^^^ In adenomas , ACTH R mRNA expression correlated closely with the expression of P450scc mRNA ( r = 0 . 8 , P = 0 . 0001 ) suggesting regulation by similar factors . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
A number of mutations in the ACTH receptor have been demonstrated in patients with this disorder which are likely to lead to loss of receptor function and thus would account for the syndrome . ^^^ Several patients , however , do not have mutations in the ACTH receptor gene coding region , and it can be demonstrated by segregation analysis that another distant gene must account for the disease in some of these cases . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
To elucidate the mechanism underlying the tissue specific expression of the ACTH receptor / MC2 receptor ( ACTH R ) in the adrenal cortex , we have cloned the mouse ACTH R promoter . ^^^ The analysis of the cDNA 5 ' end showed an untranslated region of 321 bp , and the ACTH R gene was demonstrated to be composed of two exons of 113 and 112 bp lying upstream of the single coding exon . ^^^ In conclusion , cell specific expression of the mouse ACTH R appears to be controlled by at least two factors . ^^^ The other as yet unknown factor binding between position 1236 bp and 908 bp acts as a strong inhibitory factor in nonadrenal steroidogenic cells , resulting in the adrenal specific expression of ACTH R . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In the present study , therefore , baboons were treated at midgestation with betamethasone to determine the effect of fetal pituitary ACTH on fetal adrenal growth , development , and ACTH receptor and P 450 enzyme messenger ribonucleic acid ( mRNA ) levels . ^^^ Moreover , there was approximately a 95 % decrease ( P < 0 . 01 ) in fetal adrenal expression of ACTH receptor , P 450 cholesterol side chain cleavage , and P 450 17alpha hydroxylase 17 / 20 lyase mRNA levels after betamethasone administration . ^^^ We conclude that fetal pituitary ACTH is necessary for the growth and development of fetal and definitive cortical zones and the marked coordinated increase in ACTH receptor and maintenance of P 450 cholesterol side chain cleavage / P 450 17alpha hydroxylase 17 / 20 lyase expression in the baboon fetal adrenal gland during the first half of gestation . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In situ localization of ACTH receptor like mRNA in molluscan and human immunocytes . ^^^ These findings suggest that the ACTH receptor gene has been highly conserved during evolution . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Ovine adrenocortical cells expressed one major ACTH receptor transcript of 3 . 6 kb and three minor ones of 4 . 2 , 1 . 8 and 1 . 3 kb . ^^^ Testosterone did not modify , while high concentrations of 17 beta estradiol decreased , ACTH receptor mRNA levels . ^^^ Treatment of cells with aminoglutethimide ( an inhibitor of steroidogenesis ) resulted in a dose dependent decrease in ACTH receptor mRNA levels , which was prevented by concomitant treatment with dexamethasone . ^^^ Treatment with ACTH also increased ACTH receptor mRNA levels more than twofold . ^^^ Neither dexamethasone nor ACTH modified ACTH receptor mRNA half lives . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In a previous study we reported that constitutive activating point mutations of the ACTH receptor ( ACTH R ) gene , a member of the G protein coupled receptor superfamily , were not present in hormone secreting and nonsecretory adrenocortical neoplasms . ^^^ In this study , we investigated whether allelic loss of the ACTH R gene is present in sporadic adrenal tumors . ^^^ We identified a PstI polymorphism in the promoter region 3 kilobases upstream of the coding region of the ACTH R gene . ^^^ Using this polymorphism , we analyzed loss of heterozygosity ( LOH ) of the ACTH R gene in 20 informative cases with benign and malignant adrenocortical tumors . ^^^ Analysis of the flanking region of the ACTH R using the polymorphic microsatelite marker D18S37 and D18S40 showed that this deletion was confined to the ACTH R gene . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Corticosterone response to BrdU was partially reversed by the ACTH receptor antagonist corticotropin inhibiting peptide ( CIP ) , and aldosterone response by the arginine vasopressin ( AVP ) V 1 receptor antagonist [ amino Pen 1 , Val 4 , D Arg 8 ] vasopressin ( AVP A ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In adrenocortical cells , the levels of expression of the Gs protein and ACTH receptor are decreased when the cells are deprived of ACTH and angiotensin 2 ( ANG 2 ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The orphan nuclear receptor steroidogenic factor 1 ( SF 1 ) is involved in the transcriptional regulation of all the steroid hydroxylase genes , and also regulates the transcription of the genes for Mllerian Inhibitory substance ( MIS ) , alpha subunit of glycoprotein hormone , LHbeta , oxytocin , GnRH receptor , ACTH receptor , prolactin receptor , DAX 1 , and steroidogenic acute regulatory protein . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The chicken MC 2 R mRNA is expressed in the adrenal and spleen , suggesting that the receptor mediates both endocrine and immunoregulatory functions of ACTH in the chicken . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH receptor mutation in a girl with familial glucocorticoid deficiency . ^^^ This mutation creates a new restriction enzyme site in the ACTH receptor gene , allowing accurate characterisation of the mutation without DNA sequencing . ^^^ Interestingly , she has a tall stature , a clinical finding reported in several children who have ACTH insufficiency and mutations of the ACTH receptor gene . ^^^ We suggest that mutation analysis of the ACTH receptor gene be considered in children with clinical features of FGD and tall stature . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The selective ACTH receptor antagonist corticotropin inhibiting peptide ( 10 [ 6 ] M ) annulled corticosterone response to 10 ( 9 ) M ACTH , but not to 10 ( 7 ) M PP . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Human ACTH hypersensitivity syndrome associated with abnormalities of the ACTH receptor gene . ^^^ OBJECTIVE : Activating mutations of the ACTH receptor have not been previously described . ^^^ We also examined biological activity of her circulating blood ACTH using bovine adrenocortical cell suspensions and ACTH receptor gene structure by Northern blotting analysis . ^^^ The ACTH receptor coding region was amplified by polymerase chain reaction using the leucocyte genomic DNA . ^^^ There were two base mutations ; cysteine 21 > arginine and serine 247 > glycine in the sequences coding for the first extramembranous N terminal domain and the third extramembranous loop of the ACTH receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The recent cloning of the ACTH receptor ( ACTH R ) gene allows investigation of the tissue localization and relative abundance of ACTH R mRNA in normal and neoplastic adrenal cortex . ^^^ Using in situ hybridization ( ISH ) we studied the expression of ACTH R mRNA in four adult adrenals of brain dead patients , two cortisol producing adenomas ( CPA ) , three aldosterone producing adenomas ( APA ) , one non functional adenoma ( NFA ) , and three carcinomas . ^^^ In adult adrenals , messenger RNA encoding ACTH R was localized in all three zones of the adrenal cortex , in accordance with the stimulatory role of ACTH on mineralocorticoid , glucocorticoid and adrenal androgen secretion . ^^^ All CPAs and APAs expressed significant levels of ACTH R mRNA whereas an NFA showed low expression of ACTH R mRNA . ^^^ Two of three adrenocortical carcinomas expressed ACTH R mRNA . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We have previously shown that the promoter of the human ACTH receptor ( ACTH R ) contains , at 35 bp , a binding site for the steroidogenic factor 1 ( SF 1 ) , an orphan nuclear receptor which could be responsible for the transcriptional activity of this promoter . ^^^ These results demonstrate that the SF 1 binding element present in this fragment is required for the basal promoter activity of the human ACTH R gene . ^^^ In addition , other binding elements located upstream from this characterized SF 1 binding site are involved in the full basal promoter activity of the human ACTH R since transfection studies with a longer p ( 1017 / +22 ) GH construct resulted in a higher GH release than with the p ( 56 / +22 ) GH construct . . ^^^ A steroidogenic factor 1 binding element is essential for basal human ACTH receptor gene transcription . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In summary , adrenal cells treated with ACTH results in a significant increase in the ratio of B / A in the ZF owing a noncompetitive inhibition of the 11 beta HSD 2 via the ACTH receptor . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Vasoactive intestinal peptide stimulates rat adrenal glucocorticoid secretion , through an ACTH receptor dependent activation of the adenylate cyclase signaling pathway . ^^^ A VIP receptor antagonist and the ACTH receptor antagonist corticotropin inhibiting peptide annulled both adrenocortical cell responses to VIP , while the protein kinase ( PKA ) inhibitor H 89 blocked only corticosterone response . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The ACTH receptor antagonist corticotropin inhibiting peptide ( 10 ( 6 ) M ) blocked corticosterone response of dispersed cells to 10 ( 9 ) M ACTH but not to 10 ( 7 ) M galanin ; conversely , the specific protein kinase A inhibitor H 89 ( 10 ( 5 ) M ) annulled the secretory response to both ACTH and galanin . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Constitutive activation of the ACTH receptor G protein cAMP signal cascade does not play a role in adrenal tumor formation . ^^^ Conversely , deletions of the ACTH receptor gene have been recently found in undifferentiated adenomas and in aggressive adrenocortical carcinomas . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH receptor , ACTH receptor anomaly , and familial glucocorticoid deficiency ] . ^^^ After the cloning of ACTH receptor or melanocortin 2 receptor ( MC 2R ) cDNA , several kinds of mutations in the receptor genes have been reported . ^^^ However , the apparently normal ACTH receptor gene in some affected children suggests that the etiology of FGD is heterogeneous . ^^^ In this short review , we describe the recent advances in the molecular biology of ACTH receptor genes , its post receptor signal transduction in the adrenocortical cells , and the molecular genetics of the FGD and a related syndrome , Allgrove syndrome . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH receptor ( ACTH R ) mRNA , normalized to adrenal mass or to total RNA , was not influenced by FR ( 1 . 5 mo ) . ^^^ However , adrenal ACTH R mRNA , as well as adrenal mass , per unit body weight was greater in FR than in AL rats ( diet main effect , P < 0 . 001 ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Low levels of ACTH receptor messenger RNA were also detectable in the tumor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
As ACTH stimulates the secretion of both AAs and F , it is possible that the discordant relationship of these hormones in MMD patients results from a defect of adrenocortical ACTH receptor function or postreceptor signaling or subsequent biochemical events . ^^^ Furthermore , the molecular abnormality seen in MMD patients may suggest that the mechanism underlying the frequently observed discordances in the secretion of glucocorticoids and AAs ( e . g . adrenarche , surgical trauma , severe burns , or intermittent glucocorticoid administration ) are explainable solely via an alteration in the function of the ACTH receptor or postreceptor signaling . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We studied four kindreds with HGD and four kindreds with AS for abnormalities of the ACTH receptor ( ACTHR ) gene . ^^^ In vitro expression of the mutated ACTHR in mouse melanoma M 3 cells showed that at a medium ACTH concentration of 3 nM , cells transfected with the wild type ACTHR produced twofold and threefold , respectively , of the amount of intracellular cAMP when compared to cells transfected with the ACTHR carrying the Pro273His and the Ser74Ile mutation , respectively , confirming that HGD in this kindred is caused by loss of function mutations of the ACTHR . ^^^ Genetic heterogeneity of adrenocorticotropin ( ACTH ) resistance syndromes : identification of a novel mutation of the ACTH receptor gene in hereditary glucocorticoid deficiency . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Since melanocortin receptors ( MCR ) are involved in some actions of agouti , we next determined whether agouti ' s antilipolytic effect is exerted through competitive antagonism of the ACTH receptor ( MCR 2 ) . ^^^ Forskolin ( 1 microM ) , an adenylate cyclase activator , induced a 48 % increase in lipolysis in human adipocytes ( P < 0 . 05 ) ; this effect was reversed by 100 nM agouti ( P < 005 ) , demonstrating that the antilipolytic effect of agouti is distal to the ACTH receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Several mutations in the coding exon of the ACTH receptor ( MC2R ) gene have been reported in cases of familial glucocorticoid deficiency or FGD . ^^^ Patients in these families present the typical clinical features of FGD , but no mutation was found in the coding exon of the ACTH receptor . ^^^ Exclusion of the adrenocorticotropin ( ACTH ) receptor ( MC2R ) locus in some families with ACTH resistance but no mutations of the MC2R coding sequence ( familial glucocorticoid deficiency type 2 ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
However , a specific mechanism which couples ACTH receptor activation to increased intracellular calcium concentration in the adrenal cortical cell has not been elucidated . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The adrenocorticotropin receptor or ACTH R which is the type 2 among the melanocortin receptor family is almost exclusively expressed in the adrenal cortex , reflecting a high degree of tissue specificity . ^^^ Three putative SF 1 binding sites are present in the sequence of the human ACTH R gene promoter at 35 ( SF 35 ) , 98 ( SF 98 ) and 209 ( SF 209 ) . ^^^ SF 1 and the transcriptional regulation of the human ACTH receptor gene . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Recently , AG has been shown to inhibit ACTH receptor ( ACTH R ) mRNA expression in ovine adrenocortical cells in a time dependent fashion . ^^^ To investigate whether ACTH R down regulation will also be induced in tumor cells , we studied the effect of AG on ACTH R expression in the human NCI h 295 adrenocortical carcinoma cell line , which expresses functional ACTH receptors and produces steroids of the glucocorticoid , mineralocorticoid and androgen pathway . ^^^ After 48 h , cells were harvested , and total RNA was extracted , electrophoresed , blotted and hybridized with a human ACTH R cDNA probe . ^^^ AG significantly suppressed the baseline ACTH R mRNA expression in a dose dependent fashion ( 300 microM AG , 5+ / 1 % ; 30 microM AG , 64+ / 1 % ; 3 microM AG , 108+ / 19 % compared with control cells , 100+ / 11 % ) . ^^^ The reduced ACTH R mRNA expression was paralleled by low ACTH induced cAMP accumulation indicating reduced expression of the ACTH R protein . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
These mutants present complex phenotypes in which the activity of Gbeta / gamma is impaired , ACTH receptor gene expression is markedly diminished , and ACTH responsive adenylyl cyclase activity is lost . ^^^ In this study , we have tested the hypothesis that the impairment in Gbeta / gamma activity is responsible for the loss of ACTH receptor gene expression and ACTH responsive adenylyl cyclase activity . ^^^ Transfection of one of the mutant clones with expression vectors encoding either Gbeta 1 or Gbeta 2 together with Ggamma 2 increased ACTH receptor expression and restored ACTH responsive adenylyl cyclase activity . ^^^ These results thus support the hypothesis that the impairment in Gbeta / gamma activity is responsible for the loss of ACTH receptor expression . ^^^ A luciferase reporter plasmid driven by the proximal promoter region of the mouse ACTH receptor gene was expressed poorly in the mutants compared with parental Y 1 cells , suggesting that the Gbeta / gamma defect compromised transcriptional activity at the proximal promoter region of the ACTH receptor gene . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
They also stress that this side effect of CIP must be taken into account in interpreting the results of investigations on the adrenal cortex , where CIP has been employed as an ACTH receptor antagonist . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
By performing a 3 ' deletion analysis on the ACTH R promoter construct [ 1805 / +105 ] in the mouse adrenocortical cell line Y 1 , we have investigated the possibility of alternative transcriptional initiation downstream from the identified murine initiation site . ^^^ Site directed mutagenesis of this SF 1 binding site does not disable the promoter , suggesting that another factor overlapping this site may be responsible for maximal activity of the ACTH R . . ^^^ Analysis of the first exon of the murine ACTH receptor gene . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
It is expressed in the adrenal cortex and is hence considered to be the ACTH receptor . ^^^ A DNA fragment , was obtained using primers based on the bovine ACTH receptor ( MC 2 R ) sequence . ^^^ Expression of ACTH receptors ( MC 2 R and MC 5 R ) in the glomerulosa and the fasciculata reticularis zones of bovine adrenal cortex . ^^^ The MC 2 receptor ( MC 2 R ) preferentially binds ACTH . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The entire ACTH receptor ( ACTH R ) cDNA was amplified by RT / PCR from mouse Y 1 adrenocortical cells , subcloned into the pMOSBlue T vector , sequenced and inserted into the pSVK 3 mammalian vector to obtain pSVACTHR . ^^^ Genomic integration of pSVACTHR and transcription of ACTH R cDNA were checked by Southern blot and RT / PCR respectively . ^^^ Expression of active ACTH R protein was tested by measuring cAMP production in response to ACTH . ^^^ Two ACTH R expressing transfectants ( clones 03 and 07 ) increased cAMP accumulation in response to ACTH . ^^^ Apparently , the ACTH R in Balb 3T3 cells induces the c fos gene by a pathway independent of cAMP / protein kinase A and ERK / MAP Kinase . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The glucocorticoid secretagogue effect of 10 ( 8 ) M PP was blocked by the protein kinase A ( PKA ) unhibitor H 89 , but not by the ACTH receptor antagonist corticotropin inhibiting peptide ( CIP ) Autoradiography showed the presence of [ 125I ] PP binding sites in the inner zones of rat and human adrenal cortex , which were not displaced by NPY , PYY , ACTH or CIP . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
VIP seems to act through the VIP and / or PACAP receptor while PHI acts , directly or by sensitivity increase , through the ACTH receptor . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We previously reported that ACTH receptor ( ACTH R ) mRNA is expressed in cortisol secreting adrenal tumors , with significant differences between adenomas and carcinomas . ^^^ The level of ACTH R mRNA was evaluated by competitive RT PCR using a non homologous competitor . ^^^ ACTH R gene was expressed in all tissues . ^^^ All APA showed highest ACTH R mRNA levels . ^^^ Despite signs of individual heterogeneity , the level of ACTH R transcripts was reduced in carcinomas . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Low levels of ACTH receptor mRNA were also detectable in the tumor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In the present study , we characterized two new SF 1 binding sites , SF 209 and SF 98 , in the promoter of the human ACTH receptor ( hACTH R ) gene . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Molecular biology showed a composite heterozygotism for the ACTH receptor gene . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Two of these 3 patients were studied by immunohistochemistry of steroidogenic enzymes and for the gene expression of ACTH receptor by Northern blot analysis . ^^^ ACTH receptor messenger RNA was not detected in virilizing tumor tissues , whereas it was expressed in attached adrenal tissues . ^^^ CONCLUSIONS : The lack of response to ACTH is the result of a deficiency of ACTH receptor expression in the virilizing tumor cells . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We have shown that ACTH receptor mRNA expression and steroidogenesis were increased in the transitional zone and decreased in the fetal zone of the baboon fetal adrenal in the second half of gestation . ^^^ Thus , we proposed that there is a divergence in ACTH receptor mediated zone specific steroidogenesis within the fetal adrenal during mid to late gestation . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Several missense mutations of the ACTH receptor ( MC 2 R ) gene have been associated with the autosomal recessive syndrome of familial glucocorticoid deficiency . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Autoradiography evidenced abundant [ 125I ] GIP binding sites exclusively in the inner adrenocortical layers , and the computer assisted densitometric analysis of autoradiograms demonstrated that binding was displaced by cold GIP , but not by either ACTH or the selective ACTH receptor antagonist corticotropin inhibiting peptide ( CIP ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Linkage analysis , using specific polymorphic markers , excluded the involvement of the ACTH receptor but not thyrotropin receptor ( TSHR ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
These results suggest the lymphocyte ACTH receptor is the Melanocortin 5 receptor and the receptor is internalized by endocytosis to deliver ligand to the lysosome . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The ACTH receptor antagonist corticotropin inhibiting peptide ( 10 ( 6 ) M ) annulled corticosterone response of ZF / R cells to ACTH ( 10 ( 9 ) M ) , but not to orexins ( 10 ( 8 ) M ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH receptor gene analysis revealed no mutations in the ACTH receptor coding region . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The response of the cultured theca cells was more acute than that of the adrenocortical cells , possibly reflecting the propensity of the LH receptor to desensitize rapidly , unlike the ACTH receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The receptor MC 2 ( ACTH receptor ) almost exclusively expressed in the adrenal cortex whereas MC 5 R is expressed in several organs including the adrenal cortex . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We have investigated the effects of restriction of placental growth on foetal adrenal growth and adrenal expression of mRNAs for Insulin like Growth Factor 2 ( IGF 2 ) , the IGF binding protein IGFBP 2 , Steroidogenic Factor 1 ( SF 1 ) and adrenocorticotrophic hormone ( ACTH ) receptor ( ACTH R ) and the steroidogenic cytochrome P 450 enzymes : cholesterol side chain cleavage ( CYP11A1 ) , 17alpha hydroxylase ( CYP 17 ) and 21 hydroxylase ( CYP21A1 ) ; and 3beta hydroxysteroid dehydrogenase / Delta5Delta4 isomerase ( 3betaHSD ) . ^^^ Adrenal ACTH R mRNA levels were also lower whilst CYP11A1 mRNA levels were increased ( P < 0 . 005 ) in the PR group . ^^^ Differential effects of placental restriction on IGF 2 , ACTH receptor and steroidogenic enzyme mRNA levels in the foetal sheep adrenal . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In FGD , several missense mutations within the coding region of the ACTH receptor ( MC 2 R ) have been identified in some , but not all patients , and segregation analyses and functional studies in a Y 6 cell expression system confirmed that these mutations cause the disease . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Isolated glucocorticoid deficiency and ACTH receptor mutations . ^^^ The etiological involvement of the ACTH receptor gene in isolated glucocorticoid deficiency has been recently established in many , but not all , affected families . ^^^ Several naturally occurring mutations of the ACTH receptor gene have been identified to date and have helped illuminate the mechanisms of ligand binding and signal transduction by this receptor . ^^^ Discovery of the molecular defect ( s ) responsible for isolated glucocorticoid deficiency in cases with a normal ACTH receptor gene coding region and for the triple A syndrome ( adrenal insufficiency , alacrima , achalasia ) will hopefully provide further insight into the mechanisms of adrenocortical function and will increase the prospect of new therapeutic approaches . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Here we report a 3 yr old girl with isosexual pseudoprecocious puberty due to an ovarian steroid tumor whose adrenal cell origin was determined by the presence of messenger ribonucleic acid ( mRNA ) of adrenal specific steroidogenic P 450 enzymes ( P450c11 and P450c21 ) and ACTH receptor ( ACTHR ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Mutants isolated from the Y 1 mouse adrenocortical tumor cell line ( clones 10r 9 and 10r 6 ) are resistant to ACTH because they fail to express the melanocortin 2 receptor ( MC2R ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Adrenal glucocorticoid secretion is regulated by adrenocorticotropic hormone ( ACTH ) acting through a specific cell membrane receptor ( ACTH R ) . ^^^ The ACTH R is a member of the G protein superfamily coupled receptors and belongs to the subfamily of melanocortin receptors . ^^^ The ACTH R is mainly expressed in the adrenocortical cells showing a restricted tissue specificity , although ACTH is recognized by the other four melanocortin receptors . ^^^ The cloning of the ACTH R was followed by the study of this gene in human diseases such as familial glucocorticoid deficiency ( FGD ) and adrenocortical tumors . ^^^ This disorder has been ascribed to an impaired adrenal responsiveness to ACTH due to a defective ACTH R , a defect in intracellular signal transduction or an abnormality in adrenal cortical development . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Regulation by adrenocorticotropin ( ACTH ) , angiotensin 2 , transforming growth factor beta , and insulin like growth factor 1 of bovine adrenal cell steroidogenic capacity and expression of ACTH receptor , steroidogenic acute regulatory protein , cytochrome P450c17 , and 3beta hydroxysteroid dehydrogenase . ^^^ The purpose of this study was to evaluate the time course effect of a 36 h treatment with ACTH ( 10 ( 8 ) M ) , transforming growth factor beta 1 ( TGFbeta 1 ; 10 ( 10 ) M ) , angiotensin 2 ( AngII ; 10 ( 7 ) M ) , and insulin like growth factor 1 ( IGF 1 ; 10 ( 8 ) M ) on the steroidogenic capacity of bovine adrenocortical cells ( BAC ) and on messenger RNA ( mRNA ) levels of ACTH receptor , cytochrome P450c17 , 3beta hydroxysteroid dehydrogenase ( 3betaHSD ) , steroidogenic acute regulatory protein ( StAR ) , and StAR protein . ^^^ ACTH , IGF 1 , and AngII increased ACTH receptor mRNA , but the opposite was observed after TGFbeta 1 treatment . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Adrenocorticotropic hormone receptor ( ACTHR ) is expressed predominantly in the adrenal glands , and its expression is upregulated by its own ligand , ACTH , via a cAMP dependent pathway . ^^^ In the present study , we characterized the 5 ' regulatory region of human ACTHR gene to elucidate the molecular mechanisms underlying its adrenal specific and ACTH / cAMP dependent expression . ^^^ Adrenocorticotropic hormone receptor ( ACTHR ) is expressed predominantly in the adrenal glands , and its expression is upregulated by its own ligand , ACTH , via a cAMP dependent pathway . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Novel mutations of the ACTH receptor gene in a female adult patient with adrenal unresponsiveness to ACTH . ^^^ Direct sequencing and allele specific amplification revealed two novel mutations in the ACTH receptor gene . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Mutations of the ACTH receptor gene in a new family with isolated glucocorticoid deficiency . ^^^ Mutations of the ACTH receptor gene have been reported in several families with IGD . ^^^ We have amplified and directly sequenced the entire intronless ACTH receptor gene in a new family with IGD . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The actions of ACTH are mediated by its specific membrane receptor ( ACTH R ) . ^^^ The human ACTH R gene was recently cloned , allowing systematic determination of its sequence , expression and function in adrenal tumorigenesis . ^^^ The presence of oncogenic mutations of the ACTH R gene in adrenocortical tumors has been reported . ^^^ Direct sequencing of the entire coding region of the ACTH R gene of sporadic adrenocortical adenomas and carcinomas did not reveal constitutive activating mutations , indicating that this mechanism is not frequent in human adrenocortical tumorigenesis . ^^^ Recent studies demonstrated allelic loss of the ACTH R gene in a subset of sporadic adrenocortical tumors using a PstI polymorphism located in the promoter region of the ACTH R gene . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
PATIENTS AND METHODS : Five patients with a clinical diagnosis of FGD are described in whom the disorder resulted from a variety of novel or previously described missense or nonsense mutations of the ACTH receptor ( MC 2 R ) . ^^^ CONCLUSIONS : These findings indicate that ACTH resistance resulting from a defective ACTH receptor may be associated with abnormalities of cartilage and / or bone growth independently of the GH IGF 1 axis , but probably dependent on ACTH actions through other melanocortin receptors . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The results suggest that there is a reduction in adrenal ACTH receptor number or affinity , with a high basal production rate in vivo maintaining the elevated plasma cortisol levels . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
While the mechanisms of tumorigenesis for adrenocortical neoplasms remain unknown , several genes , such as Gsalpha , ACTH receptor ( MC 2 R ) , p 53 , and p 16 tumor suppressor genes , are considered to be candidates for adrenocortical neoplasms . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In the present study , we show direct evidence that human aortic endothelial cells possess the ACTH receptor . 11beta Dehydrogenation , converting cortisol to its inactive metabolite , cortisone , mediated by vascular 11beta hydroxysteroid dehydrogenase type 2 is essential for the control of vascular tone , and the reduced activity may be relevant to the pathogenesis of hypertension . ^^^ We found that ACTH ( 1 24 ) dose dependently decreased the gene expression and enzyme activity of 11beta hydroxysteroid dehydrogenase type 2 in these cells , and the decrease was partially abolished by a selective ACTH receptor antagonist . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In FGD type 1 , ACTH receptor mutations have been described and are responsible for the loss of function of the receptor , leading to the ACTH unresponsiveness . ^^^ Patients with FGD type 2 show the same phenotype as in the previous syndrome but no mutation of the ACTH receptor has been reported in these cases . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The cortisol response to 10 ( 8 ) mol / L orexin A was unaffected by the ACTH receptor antagonist corticotropin inhibiting peptide , but was abolished by either SQ 22536 or the protein kinase A inhibitor H 89 . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH receptors exhibited a dual response since after 14 days of permanent stress MC 2 R showed a slight reduction while MC 5 R was still up regulated . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Functional expression of the human ACTH receptor gene . ^^^ The ACTH receptor is the type 2 ( MC2R ) among the melanocortin receptor family and is expressed almost exclusively in the adrenal cortex . ^^^ Moreover , we have found that the expressed hMC2R in M 3 cells showed similar ACTH binding affinity and coupling to adenylate cyclase as the MC2R of normal human adrenal cells , contrarily to most of the other expression cell models . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Cells derived from the tumor of founder 1 ( ATC 1 ) were grown in presence of forskolin to maintain ACTH receptor expression and were tested for ACTH responsiveness by immunocychemistry and northern blot analyses . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The human ACTH receptor ( ACTH R ) gene consists of two exons ; the first encodes the 5 ' untranslated region ( UTR ) and the second encodes part of the 5 ' UTR , the entire coding region , and the whole of the 3 ' UTR . ^^^ While investigating the transcription initiation site of the human ACTH R gene by 5 ' rapid amplification of cDNA ends , we found a 157 bp alternate exon in the 5 ' UTR . ^^^ This newly identified exon was irrelevant to the alternate exon in the mouse ACTH R gene which we reported previously . . ^^^ Alternate exon in the 5 ' untranslated region of the human ACTH receptor gene . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
To further understand the relative roles of the pituitary gland and ACTH in the regulation of mRNAs encoding proteins that are essential for adrenal development , we investigated the effects of , first , an ACTH infusion and labour in intact fetuses and , secondly , the effect of an ACTH infusion to fetuses with and without a pituitary gland , on the relative abundance of the mRNA encoding for the ACTH receptor ( MC2R ) , steroidogenic factor 1 ( SF 1 ) , cholesterol side chain cleavage enzyme ( P 450 ( scc ) ) , 3beta hydroxysteroid dehydrogenase ( 3betaHSD ) and 17alpha hydroxylase ( P 450 ( C 17 ) ) in the fetal adrenal gland . ^^^ ACTH ( 1 24 ) infusion ( 14 . 7 pmol / kg per h ) to intact fetuses was without effect on the abundance of mRNA encoding MC2R and SF 1 , irrespective of whether the infusion was given for 18 ( 115 132 days of gestation ) or 32 days ( 115 days to term ( 147 days of gestation ) ) . ^^^ Surprisingly , the mRNA for MC2R and SF 1 did not appear to be regulated by ACTH in the late gestation ovine fetus , though a pituitary dependent factor may be involved in the regulation of SF 1 mRNA abundance . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The data also demonstrate the expression of MC 5 R protein on rat lymphocytes , thus , supporting the hypothesis that MC 5 R is the ACTH receptor on lymphocytes . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH receptor expression , regulation and role in adrenocortial tumor formation . ^^^ The regulation of the ACTH receptor gene is unique in that it is up regulated by its own ligand , ACTH . ^^^ Ligand induced up regulation of ACTH receptor expression may be an important adaptive process directed towards optimizing adrenal responsiveness to ACTH in the context of physiological stress and the maintenance of metabolic homeostasis in which the adrenals play a pivotal role . ^^^ Since the cloning of the promoter region of the ACTH receptor , considerable progress in the understanding of the regulatory processes has been made . ^^^ The effects of ACTH on ACTH receptor expression is dependent on cAMP , probably mediated through AP 1 . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In the present study , we have examined the developmental pattern of ACTH receptor ( ACTH R ) expression during the latter half of pregnancy and in neonatal and adult life . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Constitutive activation of the ACTH receptor G protein cAMP signal cascade does not play a role in adrenal tumour formation . ^^^ Conversely , deletions of the ACTH receptor gene have recently been found in undifferentiated adenomas and in aggressive adrenocortical carcinomas , and , more recently , confirmed in a larger series of tumours . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The binding of 125I labeled [ Phe 2 , Nle 4 and Ala 24 ] ACTH ( 1 24 ) to two transformed clones of mammalian cells expressing the guinea pig ACTH receptor was also competitively inhibited by ASIF and BNP . ^^^ Overall , the findings clearly demonstrated that ASIF and BNP suppressed the adrenocortical function and inhibited ACTH for their antagonistic action against ACTH primarily at the ACTH receptor site . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Familial glucocorticoid deficiency is one of these syndromes in which about half of all cases have inactivating mutations of the ACTH receptor . ^^^ The remaining patients with this syndrome have defects in one or more other as yet unidentified genes that are unlinked to the ACTH receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Angiotensin 2 type 1 receptor and ACTH receptor expression in human adrenocortical neoplasms . ^^^ We investigated the type 1 Ang 2 receptor expression in adrenocortical tissues to define its regulation in adrenocortical neoplasms and to compare its expression with that of the ACTH receptor ( ACTH R ) . ^^^ ACTH receptor mRNA followed a similar pattern ( CPA 178 + / 17 , APA 196 + / 30 , NFA 0 % , carcinomas 56 + / 11 % ) with a good correlation between Ang 2 type 1 receptor and ACTH R mRNA of r = 0 . 692 , P = 0 . 0019 . ^^^ CONCLUSIONS : Angiotensin 2 type 1 receptor and ACTH receptor expression seems to be correlated with the functional status of adrenocortical tumours , suggesting regulation by similar factors . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The level of cholesterol side chain cleavage cytochrome P 450 mRNA in the salt inducible kinase overexpressing cells was markedly low compared with that in the parent , while the levels of Ad4BP / steroidogenic factor 1 , ACTH receptor , and steroidogenic acute regulatory protein mRNAs in the former were similar to those in the latter . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH receptor distribution and modulation among murine mononuclear leukocyte populations . ^^^ Murine mononuclear leukocytes express adrenocorticotropin ( ACTH ) receptors that were recognized by a monospecific antiserum to the ACTH receptor on Y 1 adrenal cells . ^^^ Helper T cells ( CD4+ T cells ) constituted the majority of ACTH receptor positive T lymphocytes . ^^^ The T lymphocyte mitogen , concanavalin A , interferon gamma , and ACTH enhanced ACTH receptor expression . ^^^ The differential distribution of ACTH receptor positive cells among specific leukocyte populations explains in part why differential cellular responses are observed and implies important regulatory functions for these receptors in the generation or regulation of immune responses . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In Crhr 1 / mice , intravenous ACTH administration failed to stimulate corticosterone secretion despite a significant upregulation of ACTH receptor mRNA levels in the adrenal cortex of these mutants . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The enhanced adrenocortical response of FR rats to ACTH does not reflect an increased expression of ACTH receptor ( ACTH R ) mRNA , because ACTH R mRNA / microg adrenal RNA and ACTH R mRNA / mg adrenal weight did not differ between ad libitum fed and FR rats at any age . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In addition , ASIF and BNP 32 , which are the proven ACTH receptor antagonists , reduced the cortisol stimulatory effect of ACTH and VIP . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Using the mouse adrenocortical Y 1 cell line we demonstrate that ACTH effectively desensitizes the cAMP response of its own receptor , the melanocortin 2 receptor ( MC2R ) , in these cells with a maximal effect between 30 and 60 min . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
OBJECTIVE : To examine whether inhibition of endogenous adrenocorticotropin ( ACTH ) secretion in patients with Cushing syndrome affects the expression of the ACTH receptor ( ACTH R ) gene in adrenocortical adenoma and attached atrophic normal gland . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Unresponsiveness to ACTH may be due to a mutation in the ACTH receptor ; sometimes no mutation is found . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
These results led us to speculate that the overexpression of hDiminuto in the adenoma could be due to the abundant expression of ACTH receptor , as we previously described . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Familial glucocorticoid deficiency due to corticotropin ( ACTH ) resistance consists of two distinct genetic syndromes that are both inherited as autosomal recessive traits : isolated ACTH resistance ( iACTHR ) , which may be caused by inactivating mutations of the ACTH receptor ( the MC2R gene ) or mutations in an as yet unknown gene ( s ) , and Allgrove syndrome ( AS ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
To further characterize the carcinomas , telomerase activity and the expression of the ACTH receptor gene were determined . ^^^ Telomerase activity in the carcinomas resulted in levels significantly higher than in the adenomas , whereas the levels of ACTH receptor mRNA were lower in the carcinomas . ^^^ No correlation was found in the carcinomas between the levels of the ACTH receptor transcript and the loss of expression of CREB / inducible cAMP early repressor , suggesting that this alteration is not secondary to an upstream disregulation at the receptor level . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
It has been already excluded that activating mutations of the ACTH receptor or of G protein stimulator alpha sub units , affecting cAMP pathway , is involved in the tumorigenesis . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Protein levels of P450c21 and the ACTH receptor were increased in Dax 1 ( / Y ) mice and intermediate in SF 1 ( + / ) : Dax 1 ( / Y ) mice following chronic food deprivation . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Familial glucocorticoid deficiency due to the ACTH receptor gene mutations ] . ^^^ Recently , mutations in the ACTH receptor gene were identified in several families with FGD . ^^^ Interestingly and unexpectedly , the FGD patients with the ACTH receptor gene mutations were shown to be tall . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Adrenocorticotrophic hormone ( ACTH ) stimulation of sheep fetal adrenal cortex can occur without increased expression of ACTH receptor ( ACTH R ) mRNA . ^^^ In the present study , it was hypothesized that the adrenocorticotrophin hormone receptor ( ACTH R ) would be up regulated in the adrenal gland of the sheep fetus following infusion of physiological amounts of ACTH , as shown for adrenal cortical cells in culture . ^^^ Expression of specific mRNAs was determined by ribonuclease protection assay using cRNA probes directed against : ACTH R ; the steroid enzymes side chain cleavage ( P450scc ) , 3beta hydroxysteroid dehydrogenase ( 3beta HSD ) , 17apha hydroxylase ( P450c17 ) and 21beta hydroxylase ( P450c21 ) ; and beta actin . ^^^ There was no difference in ACTH R mRNA expression between ACTH and vehicle infused fetuses ( 254 + / 48 5 . 305 + / 76 arbitrary units respectively ) . ^^^ It was concluded that ACTH is able to increase plasma cortisol concentrations in the sheep fetus by up regulating cortisol synthesis in the adrenal gland , but that in vivo this does not require up regulation of ACTH R mRNA . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Difficulty in expressing the adrenocorticotrophin ( ACTH ) receptor ( melanocortin 2 receptor ; MC2R ) after transfection of various MC2R expression vectors has been experienced by many researchers . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Although ACTH signaling through adenylyl cyclase and protein kinase A is important for normal adrenal cellular physiology , there is evidence to suggest that this pathway may inhibit the growth of adrenocortical tumors , and that inactivation of the ACTH receptor may promote tumor formation . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In normal physiology , the pituitary hormone corticotropin ( ACTH ) regulates the secretion of glucocorticoids via its G protein coupled receptor ( ACTHR ) , the product of the MC2R gene . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
While no differences in preadipocyte factor 1 , the presumed marker of primitive adrenocortical cells , were detectable in the adrenals of wt and SF 1 ( + / ) mice , an increase in the ACTH receptor as well as agouti related protein was observed only in wt animals but not in the SF 1 ( + / ) mice following uADX . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Functional relationships between three novel homozygous mutations in the ACTH receptor gene and familial glucocorticoid deficiency . ^^^ Mutations of the ACTH receptor ( MC 2 R ) gene have been reported in some FGD cases , but only a few of them have been functionally studied . ^^^ The D103N mutated MC 2 R had an impaired cAMP response to physiological doses of ACTH , but the maximal response at very high concentrations of ACTH was similar to that obtained for the wild type MC 2 R . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The ACTH receptor ( MC2R ) is expressed predominantly in the adrenal cortex , but is one of five G protein coupled , seven transmembrane melanocortin receptors ( MCRs ) , all of which bind ACTH to some degree . ^^^ This assay provides excellent sensitivity in an easily assayed transient transfection system , providing a more rapid and efficient measurement of ACTH receptor activity . . ^^^ Testing of MC2R activity is difficult because most cells express endogenous MCRs ; hence , ACTH will elicit background activation of assayable reporter systems . ^^^ Inactivating mutations of MC2R lead to hereditary unresponsiveness to ACTH , also known as familial glucocorticoid deficiency ( FGD ) . ^^^ OS 3 cells transfected with a cAMP responsive luciferase reporter plasmid ( pCREluc ) were unresponsive to ACTH , but cotransfection with a vector expressing human MC2R increased luciferase activity more than 40 fold . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We investigated the expression in human adrenal tissues by Northern blot analysis and correlated these data with the expression of the adrenocorticotrophic hormone receptor ( ACTH R ) . ^^^ In APA , TSP 1 ( r = 0 . 86 , p < 0 . 01 ) and TSP 2 ( r = 0 . 88 , p < 0 . 01 ) expressions correlated closely with the expression of ACTH R . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Whilst periconceptional undernutrition ( R R and R C groups ) resulted in higher fetal plasma adrenocorticotrophic hormone ( ACTH ) at 135 146 d gestation , there was no change in the relative level of expression of the ACTH receptor ( MC2R ) , steroidogenic acute regulatory protein ( StAR ) or steroidogenic enzyme mRNAs in the fetal adrenal in late gestation . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
A naturally occurring ACTH receptor [ melanocortin 2 receptor ( MC2R ) ] mutation ( F278C ) has been identified in a subject with ACTH independent Cushing ' s syndrome . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Among these are the clinical syndromes resulting from defects in DAX 1 and SF 1 and the functional defects caused by mutations in the ACTH receptor and the StAR protein . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In neither patient were mutations found in the ACTH receptor gene . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The physiological effects of the pituitary hormone , adrenocorticotropic hormone ( ACTH ) on the adrenal are mediated by the melanocortin 2 receptor ( MC2R ) , a G protein coupled receptor ( GPCR ) that signals via adenylate cyclase to elevate intracellular cyclic AMP ( cAMP ) levels . ^^^ The mode of internalization for the endogenous MC2R in Y 1 cells was determined using radiolabelled ACTH . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH resistance in four mutant derivatives of a mouse adrenocortical tumor cell line results from a defect that reduces the activity of steroidogenic factor 1 ( SF 1 ) thereby preventing expression of the ACTH receptor and other SF 1 dependent genes . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Expression of ACTH receptor pathway genes in GIP dependent Cushing ' s syndrome ( CS ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Direct sequencing of the genomic DNA of the patients failed to reveal mutations or other defects in the coding sequence of the ACTH receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The ACTH and alpha MSH inhibitory effects on leptin secretion were mediated by activation of the MC 2 R and MC 5 R and were reversed by the MC R antagonists ACTH ( 11 24 ) and ACTH ( 7 38 ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We previously showed an ACTH receptor overexpression in APAs compared with the other adrenal tumors . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We investigated whether activating mutations in the ACTH receptor ( MC 2 R ) or G ( s alpha ) ( GNAS 1 ) genes might be involved in AIMAH genesis . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Finally , it has been suggested that certain neurotransmitters , particularly VIP , may interact with classical hormone receptors in the adrenal , notably the ACTH receptor . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In this cell line , ACTH receptor ( ACTH R ) activates contradictory pathways of growth regulation . ^^^ Second , ACTH R triggers cAMP / PKA mediated antimitogenic mechanisms comprised of Akt / PKB dephosphorylation / deactivation , c Myc protein degradation , and p 27 ( Kip 1 ) protein induction . ^^^ In conclusion , ACTH receptor lacks signaling potential sufficient to initiate a mitogenic response in Y 1 adrenocortical cells and , therefore , can not substitute for bona fide mitogens like FGF2 . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Expression levels of ACTH receptor mRNA in adrenals increased with age in the female rat , but not in the male . ^^^ Castration enhanced the level of ACTH receptor mRNA to three fold of that in intact male rats at 14 days of age , but replacement treatment with testosterone in castrated male rats lowered the elevated levels . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Expression , desensitization , and internalization of the ACTH receptor ( MC2R ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
A polymorphic form of steroidogenic factor 1 associated with ACTH receptor deficiency in mouse adrenal cell mutants . ^^^ We have described a family of adrenocortical tumor cell mutants ( including clones OS 3 , Y 6 , and 10r9 ) that are resistant to ACTH because they fail to express the gene encoding the ACTH receptor ( MC2R ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The ACTH receptor [ melanocortin type 2 receptor ( Mc2r ) ] was identified within this fetal specific group . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH receptor mRNA expression was assessed using reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ ACTH receptor mRNA was present in mouse adipose tissue , but undetectable in human adipose tissue . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
MC 1 R , found on melanocytes , is involved in pigmentation , while MC 2 R is the classic adrenocorticotropic ( ACTH ) receptor found on the adrenal cortex and adipocytes . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
TP 53 is involved in progression to carcinoma in a subset of patients and the frequency of ACTH receptor deletion needs to be more fully explored . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Daily administration of dexamethasone ( DEX ) ( 0 . 5 mg / 100 g body weight . d ) for 6 d in mice , decreased steroidogenic function of adrenal as shown by inhibition of the 36 kDa ACTH receptor protein expression , and decreased plasma corticosterone level [ control from 465 + / 35 ng / ml to 114 + / 18 ng / ml in DEX group ( P < 0 . 001 ) ] . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Simultaneously , there was an increase in the mRNAs of the ACTH receptor and of the steroid synthesizing enzymes in the fetal adrenal gland of the older , hypoxemic fetuses . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In adrenal fasciculata cells , the glucocorticoid secretion is under the control of ACTH , which binds specifically MC 2 R , the only functional melanocortin receptor described in these cells to date . ^^^ Nevertheless , using cultured bovine fasciculata adrenal cells , we report that Agrp has no antagonistic properties against ACTH at the level of MC 2 R . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The ACTH receptor ( ACTH R ) is the second member of the melanocortin ( MC 2 ) receptor family that includes five seven transmembrane G protein coupled receptors and has been shown to be predominantly expressed in the adrenal cortex . ^^^ We therefore investigated the ACTH R in normal and adenomatous human pituitary tissue . ^^^ We report here the identification of ACTH R mRNA in the human pituitary gland , which was confirmed by direct sequencing . ^^^ We studied the expression of the ACTH R in 23 normal pituitary specimens and 53 pituitary adenomas ( 22 ACTH secreting , nine GH secreting , eight prolactin secreting , one TSH secreting , one FSH secreting , 10 nonfunctioning , and two silent corticotroph adenomas ) , using the sensitive technique of real time quantitative PCR . ^^^ ACTH R mRNA was detected in all normal pituitary specimens , and in situ hybridization colocalized expression to ACTH staining cells only . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Therefore , we quantitated ACTH receptor expression in the ovine adrenal cortex during development and after manipulations to better understand the regulation of the adrenal receptor in vivo . ^^^ ACTH receptor mRNA was quantitated by ribonuclease protection assay . ^^^ RESULTS : ACTH receptor mRNA level progressively increased in fetal life ; relative changes in receptor mRNA and binding were similar ( 3 . 0 fold and 2 . 4 fold , respectively ) . ^^^ Physiologic increases in fetal plasma cortisol decreased adrenal ACTH receptor mRNA concentration , and there was a strong ( r2=0 . 76 , P < . 002 ) linear relationship between fetal plasma ACTH concentration and receptor mRNA levels . ^^^ CONCLUSION : The data suggest that developmental increases in receptor expression are part of the maturation process in the fetal adrenal and that plasma ACTH concentration plays a major role in regulating ACTH receptor mRNA levels in vivo . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We have , therefore , examined the expression and function of the ACTH receptor ( the melanocortin 2 receptor , MC 2 R ) in human and mouse primary islet tIssue and in the MIN 6 mouse insulinoma cell line . ^^^ Overall the results demonstrate that the MC 2 R is expressed in beta cells and suggest that activation of the receptor by ACTH initiates insulin secretion through the activation of PKA in association with Ca2+ influx into beta cells . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Approximately 40 % of patients with FGD have an identifiable mutation in the ACTH receptor gene . ^^^ Patients with point mutations in the ACTH receptor gene are noted to be of tall stature . ^^^ Sequence analysis of the ACTH receptor gene showed compound heterozygosity , with two previously reported mutations : S74I and T159K . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Thus , for ACTH receptor binding and activation , the amino acid residues 15 18 are important for their side chains . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Similarly , in adrenal malignancies , significantly reduced levels of expression of the ACTH receptor gene were found . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The whole pathway activated by ACTH to destabilize c Myc protein in Y 1 cells might comprise the following steps : ACTH receptor > cAMP / PKA > Akt deactivation > GSK 3 activity liberation > c Myc Thr 58 phosphorylation . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Castration enhanced the level of ACTH receptor mRNA to 3 fold of that in intact male rats at 14 days of age , but replacement treatment with testosterone in castrated male rats lowered the elevated levels . ^^^ These findings suggest that : 1 ) the hyporesponsiveness of adrenocorticosteroid in the stress hyporesponsive period of neonates might be dependent on the reduction of ACTH receptor mRNA , and 2 ) endocrine disrupting chemicals , with characters of androgens , estrogens or gonadotropin releasing hormones , might affect the responsiveness to ACTH and the ACTH receptor mRNA expression levels in adrenal cells of neonates . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Mutations in MRAP , encoding a new interacting partner of the ACTH receptor , cause familial glucocorticoid deficiency type 2 . ^^^ Mutations of the ACTH receptor ( melanocortin 2 receptor , MC2R ) account for approximately 25 % of cases of FGD . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH resistance results from a defect affecting transcription of the ACTH receptor and can be overcome by transfecting mutant cells with expression vectors encoding G beta / gamma . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Constitutive activation of the human ACTH receptor resulting from a synergistic interaction between two naturally occurring missense mutations in the MC2R gene . ^^^ Two mutations in the same allele of the ACTH receptor ( melanocortin 2 receptor , MC2R ) associated with clinical hypersensitivity to ACTH have been described in a single case report . ^^^ The co expression of the normal MC2R allele results in the retention of a normal dose response to ACTH despite the presence of constitutive activity . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The ACTH receptor has a pivotal role in the regulation of adrenal cortisol secretion . ^^^ Here , we describe a polymorphism within the transcription initiation site of the ACTH receptor promoter altering the consensus sequence from CTC to CCC . ^^^ In conclusion , we describe an ACTH receptor promoter polymorphism that results in a lower promoter activity in vitro and is associated with a lower cortisol secretion to prolonged ACTH stimulation in vivo . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Transcripts of TSH receptor , GH receptor and ACTH receptor were detected in this cell line . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The authors believe that these two molecules competed with each other at the ACTH receptor and , thus , the bioactivity of ACTH 1 39 was masked and Cushing features were not manifested in the patient . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Our data confirmed that Agrp is not an antagonist of ACTH at the level of MC 2 R and that its sustained effect on ACTH induced steroidogenesis did not involve its antagonistic properties at the level of MC 4 R . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The adrenocorticotropic hormone ( ACTH ) acts on adrenocortical cells and promotes steroidogenesis by specific binding to the ACTH ( MC 2 ) receptor ( ACTHR ) . ^^^ To gain an insight into ACTH action on local steroidogenic organs , we examined the immunohistochemical expression of ACTHR in rat adrenal glands and placentas during the mid late gestation period . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Additionally , a systematic truncation study of the adrenocorticotropin hormone ( ACTH 1 24 ) has been performed and characterized at the cloned MC2R . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
With the exception of cyp21a and mc2r genes which were constitutively expressed , most of the genes above mentioned were induced in a time and dose dependent fashion in response to ACTH or PRL while DAX 1 was repressed . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Excessive growth was described previously in some patients with FGD , many of whom were shown to have mutations in the ACTH receptor gene . ^^^ We analyzed the ACTH receptor gene in three patients with FGD and discussed the causes of excessive growth in FGD . ^^^ No mutations were detected in the coding and promoter regions of the ACTH receptor gene of one female patient who had tall stature ( + 2 . 41S . ^^^ We speculate that the major causes of excessive growth in FGD are not only from ACTH receptor mutation , but also from the action of elevated plasma ACTH . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Up regulation of the ACTH receptor ( ACTH R ) mRNA by ACTH was found to be evident in adrenocortical cells . ^^^ However , a role of in vivo ACTH on ACTH R mRNA expression in the adrenal cortex is not well understood . ^^^ In addition , so far less attention has been also paid to the regulation of ACTH R expression in adipose tissues . ^^^ We investigated the effects of hypophysectomy and in vivo administration of ACTH or dexamethasone on the level of ACTH R mRNA in the adrenal gland and adipose tissues of mice . ^^^ RESULTS : In the adrenal gland , in vivo administration of ACTH Z significantly increased the level of ACTH R mRNA to 342 % of control values , but in vivo administration of dexamethasone or hypophysectomy induced no significant alteration of ACTH R mRNA . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
In addition , high concentrations of PCB 126 might sensitize the regulation of adrenocorticotropin ( ACTH ) on the adrenocortical cells by increasing ACTH receptor levels . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
As the primary messenger generated in response to ACTH receptor activation , cAMP acts at multiple sites to produce the full steroidogenic response that includes both rapid and delayed components . ^^^ In this way , ACTH receptor activation increases cAMP and Ca ( 2+ ) in the AZF cell , yielding the full steroidogenic response . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
We hypothesized that reductions in adrenal responsiveness and ACTH receptor ( ACTH R ) expression may be mediating factors . ^^^ At approximately 138 days of gestation , fetuses were killed , and adrenals were removed for cell culture and analyses of ACTH R mRNA and protein . ^^^ The same cells were incubated overnight with medium or medium containing ACTH or forskolin ( FSK ) , followed by ACTH stimulation ( as above ) and cortisol and cellular ACTH R mRNA analyses . ^^^ HPD prevented the late gestation increase in plasma cortisol and bioactive ACTH and reduced adrenal ACTH R mRNA and protein levels by over 35 % . ^^^ ACTH R mRNA levels in cells isolated from HPD fetuses were decreased by over 60 % , whereas overnight incubation with ACTH or FSK increased levels by approximately twofold . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
BACKGROUND : The ACTH receptor ( ACTH R ) is a member of the seven transmembrane domain receptor super family . ^^^ In non functional adrenal adenomas and adrenocortical carcinomas , ACTH R expression is low . ^^^ However , no inhibitory factor for ACTH R expression has been defined to date . ^^^ The aim of this study was to investigate whether ACTH R gene transcription is affected by DAX 1 and whether this mechanism is involved in down regulation of ACTH R expression in adrenocortical tumors . ^^^ METHODS : We screened 22 adrenocortical tumors for ACTH R and DAX 1 mRNA expression by Northern blot . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
On the molecular level , NCI h 295 cells expressed higher levels of ACTH receptor ( melanocortin receptor 2 ) mRNA upon treatment , whereas cyclin E mRNA was reduced , thus reflecting a shift toward an expression pattern found in less aggressive adrenocortical tumors in vivo . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The present study addresses the regulation of cortisol release by ACTH and alpha MSH in common carp ( Cyprinus carpio ) and includes characterization of their receptors , namely , the melanocortin 2 and melanocortin 5 receptors ( MC2R and MC5R ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
CRH , alpha MSH , and ACTH also modulate expression of their cognate receptors ( CRH R 1 , MC 1 R , MC 2 R ) . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
At the adrenal itself , heightened expression of ACTH receptor ( ACTH R ) and steroid acute regulatory protein ( StAR ) appear to be important parallel changes . ^^^ This study examined how ACTH affects ACTH R and StAR mRNA expression , and cortisol production in adrenocortical cells isolated from fetuses of varying gestational age ( dGA ) . ^^^ After 3 days of culture , cells were stimulated with ACTH ( 1 24 ) , and the cells and medium were collected at different time points ( 0 , 3 , 6 , 9 , 12 , and 24 hours ) for measurement of cortisol and ACTH R and StAR mRNA . ^^^ ACTH R mRNA levels before and after ACTH were higher in the late compared to both earlier groups . ^^^ The time to peak ACTH R mRNA response was age dependent , with the 100 105 dGA cells taking longer to attain maximum levels . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The murine and human MSH receptors ( MSH Rs ) and a human ACTH receptor ( ACTH R ) were cloned . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Real time PCR was used to quantify mRNA for steroidogenic acute regulatory protein , 17alpha hydroxylase ( CYP 17 ) , 21 hydroxylase ( CYP 21 ) , cholesterol side chain cleavage ( CYP11A1 ) , 3beta hydroxysteroid dehydrogenase type 2 ( HSD3B2 ) , and the ACTH receptor . ^^^ Adrenal mRNAs for CYP 17 , CYP11A1 , and the ACTH receptor were significantly reduced in LTH fetal sheep compared with levels shown in controls . ^^^ We conclude that expression of two key steroidogenic enzymes ( CYP 17 , CYP11A1 ) regulating cortisol biosynthesis and the ACTH receptor is lower in response to LTH . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
OBJECTIVES : Although several lines of evidence suggest that the overall effects of the ACTH receptor , melanocortin 2 receptor ( MC 2 R ) , mediated signal transduction on adrenocortical growth and tumorigenesis are anti proliferative , activation of MC 2 R induces mitogens like jun , fos , and myc and activates the MAPK pathway . ^^^ However , ACTH 1 24 treatment of group B and C mice significantly reduced tumor weight in MC 2 R positive tumors in a dose dependent manner ( P = 0 . 03 ) , while no significant difference in tumor mass was observed in MC 2 R negative tumors . ^^^ CONCLUSION : MC 2 R expression is associated with a less aggressive adrenal tumor phenotype and anti proliferative effects can be amplified through stimulation with physiological doses of ACTH . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
More rarely , mutations in Gs protein ( gsp ) and the gene for ACTH receptor have been observed in ACTs . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Genetic influence of an ACTH receptor promoter polymorphism on adrenal androgen secretion . ^^^ Here we investigate the influence of an ACTH receptor promoter polymorphism affecting ACTH receptor gene transcription on ACTH dependent dehydroepiandrosterone ( DHEA ) secretion . ^^^ DESIGN : We recently reported a polymorphism within the transcription initiation site of the ACTH receptor gene promoter that alters the consensus sequence from CTC to CCC at 2 bp . ^^^ CONCLUSION : These data demonstrate that genetic variations within the ACTH receptor promoter result in decreased DHEA secretion . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Inactivating mutations of the ACTH receptor account for approximately 25 % of these cases . ^^^ The MRAP protein appears to function in the trafficking and cell surface expression of the ACTH receptor , and might indicate the existence of more widespread G protein coupled receptor trafficking mechanisms . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Immunohistochemistry showed positive staining against chromogranin A in a histological specimen obtained from the right hand adrenal gland , while the left was negative ; the left hand adrenal gland stained positive against the ACTH receptor ( MC2R ) while the right was negative . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
The aim of this study was to investigate the short term regulation of the ACTH receptor human ( h ) melanocortin receptor 2 ( MC2R ) by transfection of a c Myc tagged hMC2R in the M 3 cell line and assess its membrane expression by indirect immunofluorescence . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
CONTEXT : Mutations in MRAP , an interacting partner of the ACTH receptor , have been shown recently to cause familial glucocorticoid deficiency ( FGD ) in kindreds with confirmed FGD and no ACTH receptor mutations . ^^^ The DAX 1 , ACTH receptor ( MC2R ) , and MRAP genes were analyzed . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
GIPR presumably acts , like the ACTH receptor ( ACTHR ) , through the Gs protein / cyclic AMP / protein kinase A ( PKA ) pathway to stimulate steroidogenesis . ^^^ Expression of ACTH receptor pathway genes in glucose dependent insulinotrophic peptide ( GIP ) dependent Cushing ' s syndrome . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
These findings show the spatio temporal specific expression patterns of MC2R and MC5R in the mouse embryo and suggest that ACTH may be related to histogenesis and / or prenatal function of various tissues and organs via MC2R and / or MC5R . . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
ACTH receptor , StAR and p450c17 mRNA levels were down regulated in adrenal tissue from UN ewes . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
Our recent studies suggest that ACTH mediated increased expression of ACTH receptor ( ACTH R ) and steroid acute regulatory protein ( StAR ) may play a role in enhancing responsiveness . ^^^ Adrenals were isolated and analyzed for ACTH R and StAR mRNA , or cells were cultured for 48 h . ^^^ ACTH R mRNA levels were significantly higher in ACTH infused fetuses in both the 118 and 138 dGA groups . ^^^ These findings demonstrate that increases in circulating ACTH levels promote increased expression of ACTH R and StAR mRNA and are coupled to heightened adrenal responsiveness . . ^^^ Infusion of ACTH stimulates expression of adrenal ACTH receptor and steroidogenic acute regulatory protein mRNA in fetal sheep . ^^^
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
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Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
NA
Interacting proteins: P01189 and Q01718	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.5203439
Attempts to were made to assess the interactions of ACTH with the principal binding regions of the ACTH receptor by analysis of binding of radioactive , iodinated ACTH 1 24 . 0.5203439^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.55746891
This is the first report clearly demonstrating that the ACTH receptor binds only ACTH , but not other melanocortin peptides . . 0.55746891^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The administration of single dose of ACTH ( ACTH residues 1 39 ; 200 mU / kg , 4 ) or repeated doses of ACTH R ( ACTH in saline containing 16 % gelatin ; 15 U / kg , sc , twice daily ) reduced the decrease in adrenal DBI LI caused by hypophysectomy . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In the present work , we have studied the effects of both hormones on ACTH receptor ( ACTH R ) mRNA and binding sites . ^^^ Both HAC and BAC expressed several ACTH R transcripts . ^^^ Although in both cell types , ACTH and A 2 increased ACTH R transcripts in a time and dose dependent manner , the maximal effects were different . ^^^ Thus , ACTH at 10 ( 9 ) M enhanced 21 and 5 fold the level of ACTH R mRNA and binding sites in HAC , whereas in BAC both parameters were enhanced only 3 fold . ^^^ A 2 at 10 ( 7 ) M increased 17 and 3 . 5 fold ACTH R mRNA and binding sites in HAC , whereas in BAC , it caused only a 2 fold increase in ACTH R mRNA and a small decrease in receptor number . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
A novel mutation of the adrenocorticotropin receptor ( ACTH R ) gene in a family with the syndrome of isolated glucocorticoid deficiency , but no ACTH R abnormalities in two families with the triple A syndrome . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
A polymerase chain reaction generated mouse ACTH R probe was used to screen a mouse genomic library , and a clone of 13kb containing the entire coding sequence was isolated . ^^^ The coding sequence shows 84 % homology with the human gene at the DNA level and encodes a peptide with 89 % homology to the human ACTH R . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
To examine whether the ACTH receptor ( ACTH R ) gene could be an oncogene in human adrenocortical tumors , we amplified by the polymerase chain reaction and directly sequenced the entire exon of the ACTH R gene in 25 adrenocortical tumors ( 17 adenomas and 8 carcinomas ) and 2 adrenocortical cancer cell lines . ^^^ We conclude that activating mutations of the ACTH R gene do not represent a frequent mechanism of human adrenocortical tumorigenesis . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The melanocortin receptor family includes the melanocyte stimulating hormone receptor ( MSH R ) , adrenocorticotropic hormone receptor ( ACTH R ) , and two neural receptors , MC 3 R and MC 4 R . ^^^ In the human these receptors map to 16q24 ( MSH R ) , 18p11 . 2 ( ACTH R ) , 20q13 . 2 ( MC 3 R ) , and 18q22 ( MC 4 R ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Bovine adrenal fasciculata reticularis cells ( BAC ) expressed at least four ACTH receptor ( ACTH R ) mRNA transcripts , one major of 3 . 6 kb and three minor of 4 . 2 , 1 . 8 and 1 . 3 kb . ^^^ ACTH and A 2 increased ACTH R mRNA levels in a time and dose dependent manner . ^^^ The results indicate that regulation of ACTH R mRNA levels may be one mechanism by which ACTH and A 2 regulate adrenocortical functions . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We therefore studied the levels of ACTH R mRNA in mouse Y 1 and human NCI H 295 ( H 295 ) adrenocortical carcinoma cell lines . ^^^ ACTH induced an increase in mouse ACTH R mRNA in Y 1 cells that was time and dose dependent , increasing 6 fold over basal levels following exposure to 10 ( 8 ) M ACTH for 19 24 h . ^^^ The amount of human ACTH R mRNA in H 295 cells increased 2 4 fold following a 24 h exposure to 10 ( 8 ) M ACTH , 1 mM dbcAMP , or 10 ( 5 ) M Forskolin . ^^^ Treatment of H 295 cells with angiotensin 2 ( A 2 ) was found to dramatically increase the level of ACTH R mRNA . ^^^ These data indicate that regulation of ACTH R mRNA levels is at least one mechanism by which ACTH and A 2 elevate the number of ACTH binding sites in the adrenocortical cells . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Prolonged administration of ACTH R ( ACTH in saline containing 16 % gelatin , 15 U / kg / day , from day 7 after surgery ) to hypophysectomized rats , completely restored DBI and MDR adrenal expression to values similar to those of sham operated rats . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Northern blot analysis revealed two ACTH R mRNA species with 4 . 0 kb and 2 . 0 kb . ^^^ ACTH R mRNAs in the adenoma tissues were much more abundant than those in the normal tissues from the two patients , suggesting that the mRNA in normal adrenal tissue is either suppressed by cortisol excess or the absence of ACTH . ^^^ To examine the mechanism involved in ACTH R mRNA regulation , the changes in the receptor mRNA caused by ACTH were studied in dexamethasone treated rats . ^^^ Administration of dexamethasone for 5 days resulted in a marked decrease in ACTH R mRNA to an undetectable level . ^^^ A bolus administration of ACTH 1 24 intravenously or ACTH Z 1 24 intramuscularly to the dexamethasone treated rat did not cause any significant change in ACTH R mRNA from 0 . 5 to 12 h after the administration . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The ACTH R is a receptor that has a prominent role in mammalian physiology , but which has been notoriously difficulty to study . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In the present study , we investigated whether the constitutive and ACTH induced expression of ACTH receptor ( ACTH R ) mRNA in bovine adrenocortical cells ( BAC ) requires new protein synthesis . ^^^ The results show that cycloheximide alone , an inhibitor of protein synthesis , induced a time and dose dependent increase in the constitutive level of the ACTH R major transcript of 3 . 6 kb in BAC . ^^^ The effect of cycloheximide involved an increase in the half life and the transcription rate of the major transcript of ACTH R ( 2 and 8 . 4 fold respectively ) . ^^^ In addition , the results also demonstrated that neither the constitutive nor the ACTH induced expression of ACTH R require new protein synthesis . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
To elucidate the mechanism underlying the tissue specific expression of the ACTH receptor / MC2 receptor ( ACTH R ) in the adrenal cortex , we have cloned the mouse ACTH R promoter . ^^^ The analysis of the cDNA 5 ' end showed an untranslated region of 321 bp , and the ACTH R gene was demonstrated to be composed of two exons of 113 and 112 bp lying upstream of the single coding exon . ^^^ In conclusion , cell specific expression of the mouse ACTH R appears to be controlled by at least two factors . ^^^ The other as yet unknown factor binding between position 1236 bp and 908 bp acts as a strong inhibitory factor in nonadrenal steroidogenic cells , resulting in the adrenal specific expression of ACTH R . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We propose that the most likely molecular mechanism for the multiple ACTH R mRNA transcripts is the alternative use of polyadenylation signals . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The recent cloning of the ACTH receptor ( ACTH R ) gene allows investigation of the tissue localization and relative abundance of ACTH R mRNA in normal and neoplastic adrenal cortex . ^^^ Using in situ hybridization ( ISH ) we studied the expression of ACTH R mRNA in four adult adrenals of brain dead patients , two cortisol producing adenomas ( CPA ) , three aldosterone producing adenomas ( APA ) , one non functional adenoma ( NFA ) , and three carcinomas . ^^^ In adult adrenals , messenger RNA encoding ACTH R was localized in all three zones of the adrenal cortex , in accordance with the stimulatory role of ACTH on mineralocorticoid , glucocorticoid and adrenal androgen secretion . ^^^ All CPAs and APAs expressed significant levels of ACTH R mRNA whereas an NFA showed low expression of ACTH R mRNA . ^^^ Two of three adrenocortical carcinomas expressed ACTH R mRNA . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The ACTH receptor ( ACTH R ) has recently been cloned , allowing systematic evaluation of its expression and function in adrenal tumorigenesis . ^^^ We investigated ACTH R and P 450 side chain cleavage enzyme ( P450scc ) mRNA expression in a variety of neoplastic adrenocortical tissues by Northern blot and reverse transcriptase PCR ( RT PCR ) . ^^^ Poly A mRNA was electrophoresed , immobilized on a nylon membrane and hybridized using alpha 32P CTP labelled human ACTH R and P450scc cDNAs . ^^^ RESULTS : Mean ACTH R mRNA expression showed significant differences between groups ( P = 0 . 0001 ) , but appeared to be independent of plasma ACTH concentrations . ^^^ In adenomas , ACTH R mRNA expression correlated closely with the expression of P450scc mRNA ( r = 0 . 8 , P = 0 . 0001 ) suggesting regulation by similar factors . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In a previous study we reported that constitutive activating point mutations of the ACTH receptor ( ACTH R ) gene , a member of the G protein coupled receptor superfamily , were not present in hormone secreting and nonsecretory adrenocortical neoplasms . ^^^ In this study , we investigated whether allelic loss of the ACTH R gene is present in sporadic adrenal tumors . ^^^ We identified a PstI polymorphism in the promoter region 3 kilobases upstream of the coding region of the ACTH R gene . ^^^ Using this polymorphism , we analyzed loss of heterozygosity ( LOH ) of the ACTH R gene in 20 informative cases with benign and malignant adrenocortical tumors . ^^^ Analysis of the flanking region of the ACTH R using the polymorphic microsatelite marker D18S37 and D18S40 showed that this deletion was confined to the ACTH R gene . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We have previously shown that the promoter of the human ACTH receptor ( ACTH R ) contains , at 35 bp , a binding site for the steroidogenic factor 1 ( SF 1 ) , an orphan nuclear receptor which could be responsible for the transcriptional activity of this promoter . ^^^ These results demonstrate that the SF 1 binding element present in this fragment is required for the basal promoter activity of the human ACTH R gene . ^^^ In addition , other binding elements located upstream from this characterized SF 1 binding site are involved in the full basal promoter activity of the human ACTH R since transfection studies with a longer p ( 1017 / +22 ) GH construct resulted in a higher GH release than with the p ( 56 / +22 ) GH construct . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH receptor ( ACTH R ) mRNA , normalized to adrenal mass or to total RNA , was not influenced by FR ( 1 . 5 mo ) . ^^^ However , adrenal ACTH R mRNA , as well as adrenal mass , per unit body weight was greater in FR than in AL rats ( diet main effect , P < 0 . 001 ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Recently , AG has been shown to inhibit ACTH receptor ( ACTH R ) mRNA expression in ovine adrenocortical cells in a time dependent fashion . ^^^ To investigate whether ACTH R down regulation will also be induced in tumor cells , we studied the effect of AG on ACTH R expression in the human NCI h 295 adrenocortical carcinoma cell line , which expresses functional ACTH receptors and produces steroids of the glucocorticoid , mineralocorticoid and androgen pathway . ^^^ After 48 h , cells were harvested , and total RNA was extracted , electrophoresed , blotted and hybridized with a human ACTH R cDNA probe . ^^^ AG significantly suppressed the baseline ACTH R mRNA expression in a dose dependent fashion ( 300 microM AG , 5+ / 1 % ; 30 microM AG , 64+ / 1 % ; 3 microM AG , 108+ / 19 % compared with control cells , 100+ / 11 % ) . ^^^ The reduced ACTH R mRNA expression was paralleled by low ACTH induced cAMP accumulation indicating reduced expression of the ACTH R protein . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The adrenocorticotropin receptor or ACTH R which is the type 2 among the melanocortin receptor family is almost exclusively expressed in the adrenal cortex , reflecting a high degree of tissue specificity . ^^^ Three putative SF 1 binding sites are present in the sequence of the human ACTH R gene promoter at 35 ( SF 35 ) , 98 ( SF 98 ) and 209 ( SF 209 ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
By performing a 3 ' deletion analysis on the ACTH R promoter construct [ 1805 / +105 ] in the mouse adrenocortical cell line Y 1 , we have investigated the possibility of alternative transcriptional initiation downstream from the identified murine initiation site . ^^^ Site directed mutagenesis of this SF 1 binding site does not disable the promoter , suggesting that another factor overlapping this site may be responsible for maximal activity of the ACTH R . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We have investigated the effects of restriction of placental growth on foetal adrenal growth and adrenal expression of mRNAs for Insulin like Growth Factor 2 ( IGF 2 ) , the IGF binding protein IGFBP 2 , Steroidogenic Factor 1 ( SF 1 ) and adrenocorticotrophic hormone ( ACTH ) receptor ( ACTH R ) and the steroidogenic cytochrome P 450 enzymes : cholesterol side chain cleavage ( CYP11A1 ) , 17alpha hydroxylase ( CYP 17 ) and 21 hydroxylase ( CYP21A1 ) ; and 3beta hydroxysteroid dehydrogenase / Delta5Delta4 isomerase ( 3betaHSD ) . ^^^ Adrenal ACTH R mRNA levels were also lower whilst CYP11A1 mRNA levels were increased ( P < 0 . 005 ) in the PR group . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The hypothalamus , pituitary gland , adrenal glands , and liver were immediately obtained to determine the amounts of corticotropin releasing hormone ( CRH ) , beta endorphin , and mRNA for pro opiomelanocorticotropin ( POMC ) , the ACTH receptor ( ACTH R ) , and insulin like growth factor 1 ( IGF 1 ) . ^^^ At 1 d of age , control pigs tended to weigh more ( P = . 09 ) , have a lower expression of ACTH R mRNA ( P = . 01 ) and IGF 1 mRNA ( P = . 01 ) , and a lower CORT : MED ( P = . 04 ) than ACTH pigs . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The entire ACTH receptor ( ACTH R ) cDNA was amplified by RT / PCR from mouse Y 1 adrenocortical cells , subcloned into the pMOSBlue T vector , sequenced and inserted into the pSVK 3 mammalian vector to obtain pSVACTHR . ^^^ Genomic integration of pSVACTHR and transcription of ACTH R cDNA were checked by Southern blot and RT / PCR respectively . ^^^ Expression of active ACTH R protein was tested by measuring cAMP production in response to ACTH . ^^^ Two ACTH R expressing transfectants ( clones 03 and 07 ) increased cAMP accumulation in response to ACTH . ^^^ Apparently , the ACTH R in Balb 3T3 cells induces the c fos gene by a pathway independent of cAMP / protein kinase A and ERK / MAP Kinase . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We previously reported that ACTH receptor ( ACTH R ) mRNA is expressed in cortisol secreting adrenal tumors , with significant differences between adenomas and carcinomas . ^^^ The level of ACTH R mRNA was evaluated by competitive RT PCR using a non homologous competitor . ^^^ ACTH R gene was expressed in all tissues . ^^^ All APA showed highest ACTH R mRNA levels . ^^^ Despite signs of individual heterogeneity , the level of ACTH R transcripts was reduced in carcinomas . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The enhanced adrenocortical response of FR rats to ACTH does not reflect an increased expression of ACTH receptor ( ACTH R ) mRNA , because ACTH R mRNA / microg adrenal RNA and ACTH R mRNA / mg adrenal weight did not differ between ad libitum fed and FR rats at any age . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Adrenal glucocorticoid secretion is regulated by adrenocorticotropic hormone ( ACTH ) acting through a specific cell membrane receptor ( ACTH R ) . ^^^ The ACTH R is a member of the G protein superfamily coupled receptors and belongs to the subfamily of melanocortin receptors . ^^^ The ACTH R is mainly expressed in the adrenocortical cells showing a restricted tissue specificity , although ACTH is recognized by the other four melanocortin receptors . ^^^ The cloning of the ACTH R was followed by the study of this gene in human diseases such as familial glucocorticoid deficiency ( FGD ) and adrenocortical tumors . ^^^ This disorder has been ascribed to an impaired adrenal responsiveness to ACTH due to a defective ACTH R , a defect in intracellular signal transduction or an abnormality in adrenal cortical development . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The actions of ACTH are mediated by its specific membrane receptor ( ACTH R ) . ^^^ The human ACTH R gene was recently cloned , allowing systematic determination of its sequence , expression and function in adrenal tumorigenesis . ^^^ The presence of oncogenic mutations of the ACTH R gene in adrenocortical tumors has been reported . ^^^ Direct sequencing of the entire coding region of the ACTH R gene of sporadic adrenocortical adenomas and carcinomas did not reveal constitutive activating mutations , indicating that this mechanism is not frequent in human adrenocortical tumorigenesis . ^^^ Recent studies demonstrated allelic loss of the ACTH R gene in a subset of sporadic adrenocortical tumors using a PstI polymorphism located in the promoter region of the ACTH R gene . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The human ACTH receptor ( ACTH R ) gene consists of two exons ; the first encodes the 5 ' untranslated region ( UTR ) and the second encodes part of the 5 ' UTR , the entire coding region , and the whole of the 3 ' UTR . ^^^ While investigating the transcription initiation site of the human ACTH R gene by 5 ' rapid amplification of cDNA ends , we found a 157 bp alternate exon in the 5 ' UTR . ^^^ This newly identified exon was irrelevant to the alternate exon in the mouse ACTH R gene which we reported previously . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Adrenocorticotrophic hormone ( ACTH ) stimulation of sheep fetal adrenal cortex can occur without increased expression of ACTH receptor ( ACTH R ) mRNA . ^^^ In the present study , it was hypothesized that the adrenocorticotrophin hormone receptor ( ACTH R ) would be up regulated in the adrenal gland of the sheep fetus following infusion of physiological amounts of ACTH , as shown for adrenal cortical cells in culture . ^^^ Expression of specific mRNAs was determined by ribonuclease protection assay using cRNA probes directed against : ACTH R ; the steroid enzymes side chain cleavage ( P450scc ) , 3beta hydroxysteroid dehydrogenase ( 3beta HSD ) , 17apha hydroxylase ( P450c17 ) and 21beta hydroxylase ( P450c21 ) ; and beta actin . ^^^ There was no difference in ACTH R mRNA expression between ACTH and vehicle infused fetuses ( 254 + / 48 5 . 305 + / 76 arbitrary units respectively ) . ^^^ It was concluded that ACTH is able to increase plasma cortisol concentrations in the sheep fetus by up regulating cortisol synthesis in the adrenal gland , but that in vivo this does not require up regulation of ACTH R mRNA . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We investigated the expression in human adrenal tissues by Northern blot analysis and correlated these data with the expression of the adrenocorticotrophic hormone receptor ( ACTH R ) . ^^^ In APA , TSP 1 ( r = 0 . 86 , p < 0 . 01 ) and TSP 2 ( r = 0 . 88 , p < 0 . 01 ) expressions correlated closely with the expression of ACTH R . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In this cell line , ACTH receptor ( ACTH R ) activates contradictory pathways of growth regulation . ^^^ Second , ACTH R triggers cAMP / PKA mediated antimitogenic mechanisms comprised of Akt / PKB dephosphorylation / deactivation , c Myc protein degradation , and p 27 ( Kip 1 ) protein induction . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The ACTH receptor ( ACTH R ) is the second member of the melanocortin ( MC 2 ) receptor family that includes five seven transmembrane G protein coupled receptors and has been shown to be predominantly expressed in the adrenal cortex . ^^^ We therefore investigated the ACTH R in normal and adenomatous human pituitary tissue . ^^^ We report here the identification of ACTH R mRNA in the human pituitary gland , which was confirmed by direct sequencing . ^^^ We studied the expression of the ACTH R in 23 normal pituitary specimens and 53 pituitary adenomas ( 22 ACTH secreting , nine GH secreting , eight prolactin secreting , one TSH secreting , one FSH secreting , 10 nonfunctioning , and two silent corticotroph adenomas ) , using the sensitive technique of real time quantitative PCR . ^^^ ACTH R mRNA was detected in all normal pituitary specimens , and in situ hybridization colocalized expression to ACTH staining cells only . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
BACKGROUND : The ACTH receptor ( ACTH R ) is a member of the seven transmembrane domain receptor super family . ^^^ In non functional adrenal adenomas and adrenocortical carcinomas , ACTH R expression is low . ^^^ However , no inhibitory factor for ACTH R expression has been defined to date . ^^^ The aim of this study was to investigate whether ACTH R gene transcription is affected by DAX 1 and whether this mechanism is involved in down regulation of ACTH R expression in adrenocortical tumors . ^^^ METHODS : We screened 22 adrenocortical tumors for ACTH R and DAX 1 mRNA expression by Northern blot . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Up regulation of the ACTH receptor ( ACTH R ) mRNA by ACTH was found to be evident in adrenocortical cells . ^^^ However , a role of in vivo ACTH on ACTH R mRNA expression in the adrenal cortex is not well understood . ^^^ In addition , so far less attention has been also paid to the regulation of ACTH R expression in adipose tissues . ^^^ We investigated the effects of hypophysectomy and in vivo administration of ACTH or dexamethasone on the level of ACTH R mRNA in the adrenal gland and adipose tissues of mice . ^^^ RESULTS : In the adrenal gland , in vivo administration of ACTH Z significantly increased the level of ACTH R mRNA to 342 % of control values , but in vivo administration of dexamethasone or hypophysectomy induced no significant alteration of ACTH R mRNA . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We hypothesized that reductions in adrenal responsiveness and ACTH receptor ( ACTH R ) expression may be mediating factors . ^^^ At approximately 138 days of gestation , fetuses were killed , and adrenals were removed for cell culture and analyses of ACTH R mRNA and protein . ^^^ The same cells were incubated overnight with medium or medium containing ACTH or forskolin ( FSK ) , followed by ACTH stimulation ( as above ) and cortisol and cellular ACTH R mRNA analyses . ^^^ HPD prevented the late gestation increase in plasma cortisol and bioactive ACTH and reduced adrenal ACTH R mRNA and protein levels by over 35 % . ^^^ ACTH R mRNA levels in cells isolated from HPD fetuses were decreased by over 60 % , whereas overnight incubation with ACTH or FSK increased levels by approximately twofold . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In two cases where the lack of action of ACTH was related to an anomaly of ACTH receptor , the protein kinase activity was normal . ^^^ In the other two cases the ACTH receptor was normal , but the protein kinase activity was different from that of the normal adrenal . ^^^ Therefore , the lack of response to ACTH of some adrenocortical human tumors may be attributed either to an anomaly of the ACTH receptor or to some defect of the cAMP dependent protein kinase . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
These findings further support the hypothesis that fetal ACTH plays a role in the normal development of the adenylate cyclase catalytic portion of the ACTH receptor complex and adrenal differentiation during this critical period of fetal life . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH receptor levels in lamb adrenals at late gestation and early neonatal stages . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
At the adrenal itself , heightened expression of ACTH receptor ( ACTH R ) and steroid acute regulatory protein ( StAR ) appear to be important parallel changes . ^^^ This study examined how ACTH affects ACTH R and StAR mRNA expression , and cortisol production in adrenocortical cells isolated from fetuses of varying gestational age ( dGA ) . ^^^ After 3 days of culture , cells were stimulated with ACTH ( 1 24 ) , and the cells and medium were collected at different time points ( 0 , 3 , 6 , 9 , 12 , and 24 hours ) for measurement of cortisol and ACTH R and StAR mRNA . ^^^ ACTH R mRNA levels before and after ACTH were higher in the late compared to both earlier groups . ^^^ The time to peak ACTH R mRNA response was age dependent , with the 100 105 dGA cells taking longer to attain maximum levels . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The murine and human MSH receptors ( MSH Rs ) and a human ACTH receptor ( ACTH R ) were cloned . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Our recent studies suggest that ACTH mediated increased expression of ACTH receptor ( ACTH R ) and steroid acute regulatory protein ( StAR ) may play a role in enhancing responsiveness . ^^^ Adrenals were isolated and analyzed for ACTH R and StAR mRNA , or cells were cultured for 48 h . ^^^ ACTH R mRNA levels were significantly higher in ACTH infused fetuses in both the 118 and 138 dGA groups . ^^^ These findings demonstrate that increases in circulating ACTH levels promote increased expression of ACTH R and StAR mRNA and are coupled to heightened adrenal responsiveness . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Adrenal cell suspensions prepared from rats bearing the MtTF 4 tumor failed to increase corticosterone production when exposed to adenosine 3 ' , 5 ' cyclic monophosphate ( cyclic AMP ) or ACTH , placing the defect in these adrenals beyond the ACTH receptor site . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In vitro the lack of ACTH ' s action was related to an anomaly of ACTH receptor with normal protein kinase activity . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
These findings suggest that the anti receptor antibody recognizes the ligand binding domain of the ACTH receptor . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Expression of the ACTH receptor in individual stage 5 and 6 oocytes was monitored by radioimmunoassay of ligand stimulated cAMP production . ^^^ Size fractionation of rat adrenal poly ( A ) + RNA by sucrose density gradient centrifugation revealed that mRNA encoding the ACTH receptor was present in the 1 . 1 to 2 . 0 kilobase fraction . ^^^ This system should permit more complete characterization and expression cloning of the ACTH receptor . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
If such lymphocyte binding , as has been suggested , reflects adrenal ACTH receptor activity , these data would suggest that the glucocorticoid deficiency of Allgrove syndrome is not the result of a defect in that receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
This suggests that the defect in autonomous glands is not located at the level of the ACTH receptor , but , rather , involves the adenylate cyclase complex as a whole or its coupling to cAMP dependent protein kinase . ^^^ This points to a defect in the adenoma cells beyond the ACTH receptor . 2 ) Adrenal adenoma formation in patients with Cushing ' s syndrome is accompanied by a relative blockade of 11 beta hydroxylase activity . 3 ) By comparing the preoperative dynamic tests of the pituitary adrenal axis , the plasma ACTH concentration , the morphology of the adrenal glands , and their in vitro responsiveness , a gradual transition from pituitary to ( partial ) adrenal autonomy could be recognized in several patients . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
These findings show that anti HTCA competes with ACTH for binding to the ACTH receptor . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
These results suggest that amphibian adrenocortical cells contain only one class of ACTH receptor which recognizes the 11 24 domain of ACTH with an affinity which depends on the presence of a strong potentiator segment , located at the N terminus end of ACTH ( 1 39 ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Signal transduction in the ACTH receptor : activation by microaggregation . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
However , ACTH receptor expression by these cell populations was not static as suggested by the ability to induce receptor expression via mitogens . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In addition , cortisol modulates the mechanism by which ACTH activates fetal adrenal function , possibly through an action at the level of the ACTH receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Thus , metabolic inhibition permits demonstration of ACTH receptor binding only , unconfounded by sequestration or internalization of ligand : receptor complexes . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The variations in ACTH receptor number were associated with parallel changes on acute ACTH induced cyclic AMP production . ^^^ Thus , the effects of TGF beta on ACTH receptor content are likely another important negative action of this peptide on adrenocortical cell differentiation . ^^^ Moreover , these results suggest that regulation of ACTH receptor number may be one mechanism by which hormones and growth factors control adrenocortical differentiation . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The molecular weight of the ACTH receptor appears to be between 83 and 100 KD . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
This result indicates that the bovine adrenal ACTH receptor , whose identification and characterization have proved difficult , has an Mr of about 40 , 000 . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
An ACTH receptor on human mononuclear leukocytes . ^^^ Relation to adrenal ACTH receptor activity . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
To investigate this possibility , we measured some ACTH receptor parameters in isolated adrenocortical cells from normal and dietary protein restricted domestic fowl . ^^^ Inhibitor constants of hACTH ( 7 38 ) , calculated from Schild plots , were 3 . 16 10 10 ( 7 ) and 9 . 82 10 10 ( 7 ) M for L and N cockerel cells , respectively , thus suggesting differences in ACTH receptor function between the two treatment groups . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
This protein may well represent the long sought , adenylate cyclase linked , low affinity ACTH receptor or a portion thereof . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH receptor mediated induction of leukocyte cyclic AMP . ^^^ Immunofluorescence assays , employing an antiserum to the adrenal cell ACTH receptor , indicated that 45 % of splenocytes , 69 % of S49A cells , and less than 1 % of Molt 4 cells possess ACTH receptors . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
That this binding might result from one peptide being an `` internal image ' ' of the other was strongly suggested by the observation that antibody to the peptide that was encoded by the complementary RNA for ACTH recognized the adrenal cell ACTH receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
However , 9 tryptophan ( O nitrophenylsulfenyl ) ACTH was 8 times more potent with fowl cells than with rat cells , thus suggesting that ACTH receptor differences exist between the two cell types . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
This effect supports the hypothesis of a direct interaction between lipopolysaccharide and the cell membrane with a concomitant distortion of the cell surface affecting the ACTH receptor sites of their environment . [ 14C ] Lipopolysaccharide binds to isolated adrenocortical cells . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Behavioral support for an ACTH receptor in the CNS . ^^^ In this report we present a series of experiments which have led us to support the notion of the presence of an ACTH receptor in the CNS . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Using immunoaffinity chromatography the ACTH receptor was purified , and the molecular structure and 125I ACTH binding characteristics were determined . ^^^ A molecular weight ( Mr ) of 225 000 was determined for the complete ACTH receptor as analyzed by sodium dodecyl sulfate ( SDS ) polyacrylamide gel electrophoresis . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The inhibitory action of vanadium compounds was also seen when cholera toxin or forskolin was used as a stimulant instead of ACTH , indicating that vanadate does not act on the ACTH receptor protein . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Our attempts to develop adrenocorticotropic hormone ( ACTH ) analogues that can be employed for ACTH receptor identification and isolation began with the synthesis of ACTH fragments containing N epsilon ( dethiobiotinyl ) lysine ( dethiobiocytin ) amide in position 25 to be used for affinity chromatographic purification of hormone receptor complexes on Sepharose immobilized avidin resins . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Characterization of the porcine ACTH receptor with the aid of a monoclonal antibody . ^^^ Monoclonal antibodies were raised against the ACTH receptor by immunization of BALB 1 c mice with porcine adrenal cortex cell membranes . ^^^ Competition and binding experiments confirmed that one of these antibodies , IV / 14 / 9 , reacted with the ACTH receptor in competition with ACTH and caused a definite ACTH like effect . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Comparison of the activity profile of additional compounds , such as des acetyl alpha MSH , ( Tyr ( 1 ) 2 ) alpha MSH , ( Trp ( For ) 9 ) alpha MSH or ( Nva 12 ) alpha MSH , in the adrenocortical and pigment cell assays led to the conclusion that alpha MSH does not exert its steroidogenic effect through a typical melanocyte type of MSH receptor , but rather through a low affinity type of ACTH receptor . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The present investigation was performed in order to study the properties of abnormal membrane function related to ACTH receptor adenylate cyclase system interaction in human ACTH unresponsive adrenocortical cancer . ^^^ These results suggest that the lack of ACTH receptor at the cell membrane surface might be responsible for ACTH unresponsiveness in the CS tissue , although an accelerated degradation of GTP could contribute to decreased activity of GTP binding protein . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Neuraminidase appeared to alter a carbohydrate containing ACTH receptor preventing ACTH binding . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
It is suggested that ACTH ganglioside interactions will participate in ACTH receptor interactions . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Ontogeny of the ACTH receptor , adenylate cyclase and steroidogenesis in adrenal . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
A specific and sensitive assay for determining the binding of adrenocorticotropin ( ACTH ) to isolated rat adipocytes has been developed and utilized to study the effect of glucocorticoids on ACTH receptor . ^^^ Our results indicate that glucocorticoids do not cause their permissive effects by specific regulation of the ACTH receptor on the adipocyte . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The data on mouse adipocyte membrane suggests that the coupling of ACTH receptor to adenylate cyclase is dependent on GTP and that catecholamine activation of adenylate cyclase is less dependent on this nucleotide . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
These results together with previous data showing that the magnitude and time course of the adrenal cAMP response to ACTH changes diurnally strongly suggest that ACTH receptor affinity or coupling with adenylate cyclase changes diurnally . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
It is suggested that p 68 may regulate the transfer of information from the occupied ACTH receptor ot the catalytic subunit of adenylate cyclase . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Existence of a specific ACTH receptor was demonstrated using 125I radioiodinated ACTH 1 24 . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The data suggest that alpha MSH at low concentrations ( less than 10 ( 7 ) mol / l ) interacts with a glomerulosa cell receptor which is distinct from the ACTH receptor but interacts with the ACTH receptor at concentrations greater than 10 ( ' 5 ) mol / l . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Both the specificity and lack of specificity of the action of this agent to influence the activity of the 3 secretagogues suggest that naloxone and possibly a naturally occurring endogenous ligand interacts with one or more membrane receptor distinct from the ACTH receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The steroid specificity of suppression of cyclic AMP ( cAMP ) induced and ACTH induced steroidogenesis were similar , suggesting that suppression is not solely the result of interference with ACTH receptor function or the induction of adenylate cyclase activity . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The effects of ions on the level of ACTH receptor mRNA were also analyzed . ^^^ ACTH receptor mRNA levels remain unaffected by either low sodium or high potassium intake . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH receptor deficient mutants of the Y 1 mouse adrenocortical tumor cell line . ^^^ As determined from Northern blot and RNase protection assays , ACTH resistance in these mutants results from the failure to accumulate ACTH receptor transcripts . ^^^ The ACTH receptor gene appears to be present in these mutants as determined by Southern blot hybridization analysis and can be activated following the growth of the mutant cells as tumors in mice , suggesting that the ACTH receptor gene is modified in a reversible manner . ^^^ These results suggest that the adenylyl cyclase system in the mutants is otherwise intact and that the failure to express ACTH receptor transcripts limits the responsiveness of these clones to the hormone . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The reason for this defect in ACTH binding remains unclear because no significant mutation in the ACTH receptor DNA sequence was detected in the MNLs of these patients . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
One day later , pigs were killed and adrenal glands obtained for ACTH receptor measurements . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The objective of this study was to investigate the presence of activating mutations of the ACTH receptor gene in benign and malignant adrenocortical tumours . ^^^ Genomic DNA was extracted from a variety of adrenocortical neoplasms from 16 patients and the entire ACTH receptor gene was then amplified by the polymerase chain reaction and sequenced . ^^^ No mutations were detected within the coding region of the ACTH receptor gene in the 16 adrenocortical tumours studied . ^^^ It is likely that mutations of the coding region of the ACTH receptor gene do not play a major role in adrenocortical tumourigenesis . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Pathogenetic mutations have been identified in the ACTH receptor gene in families with isolated familial ACTH unresponsiveness . ^^^ Whether the ACTH receptor represents the locus of the defect for the triple A syndrome is not known . ^^^ Screening for abnormalities of the ACTH receptor gene by single strand conformation polymorphism analysis revealed no abnormality . ^^^ Direct sequencing of the entire coding area of the ACTH receptor gene was also normal . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The ACTH receptor mRNA and the MSH receptor mRNA were expressed only in the adrenal and melanocytes , respectively . ^^^ For analysis of the transcriptional regulation of ACTH receptor in Y 1 cells , 1 have isolated the mouse ACTH receptor gene . ^^^ A 914 bp DNA fragment of the human ACTH receptor gene was amplified by polymerase chain reaction and used as a probe . ^^^ By comparing it with the previously reported human ACTH receptor gene and bovine ACTH receptor cDNA , the mouse homologue is intron less in its coding region , and has a potential to encode for a 296 amino acid polypeptide which possesses 88 . 9 % and 78 . 7 % identities to the human and bovine ACTH receptors , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
These results suggest that renin independent overproduction and clinically observed ACTH dependent production of aldosterone in APAs may results from the enhanced transcription of P450c11 and ACTH receptor genes . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Defects of the ACTH receptor have been suggested as a possible cause , and we have previously reported a number of novel mutations of the ACTH receptor gene in some , but not all , cases , suggesting that familial glucocorticoid deficiency may have a heterogeneous molecular etiology . ^^^ Here we report the clinical features and ACTH receptor gene analysis in four patients from different families . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Using cultured human fetal adrenal cells , we have investigated the basal secretion of cortisol and dehydroepiandrosterone sulfate ( DHAS ) and the effect of corticotropin ( ACTH ) , angiotensin 2 ( A 2 ) and transforming growth factor beta 1 ( TGF beta 1 ) on the secretion of these steroids and on the mRNA levels of ACTH receptor ( ACTHR ) , cytochrome P 450scc ( cholesterol side chain cleavage ) , P 450 17 alpha ( 17 alpha hydroxylase / 17 20 lyase ) and 3 beta HSD ( 3 beta hydroxysteroid dehydrogenase ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We now demonstrate that ACTH resistance in the Y 6 and OS 3 mutants results from the failure to express the gene encoding the ACTH receptor . ^^^ Whereas parental Y 1 cells express ACTH receptor transcripts at low levels and are stimulated by ACTH or 8 bromo cAMP to increase the accumulation of ACTH receptor transcripts approximately twofold , the Y 6 and OS 3 mutants do not express receptor transcripts either in the presence or absence of 8 bromo cAMP . ^^^ The gene encoding the ACTH receptor appears to be present in the Y 6 and OS 3 mutants , as determined by Southern blot hybridization analysis . ^^^ Moreover , in the Y 6 mutant the ACTH receptor gene appears to be silenced by a modification that is reversed following the growth of the cells as tumors in mice . ^^^ Clonal isolates of Y 6 cells grown as tumors recover the ability to express ACTH receptor transcripts at low but detectable levels and acquire the ability to respond to ACTH with increased adenylyl cyclase activity . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
TGF beta 1 alone had no effect on ACTH receptor messenger ribonucleic acid ( mRNA ) levels and was unable to reduce the strong stimulatory effects of ACTH on its own receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The complementary peptide approach has also been used to produce antibodies specific for the ACTH receptor complex . ^^^ Monospecific antibodies to the ACTH ( 1 24 ) complementary peptide caused an ACTH like steroidogenic response of cultured mouse adrenal cells , presumably by binding to the ACTH receptor , and binding was specifically inhibited by ACTH . ^^^ The ACTH receptor complex from solubilized adrenal cells was shown to consist of four subunits with M ( r ) 83 , 000 , 64 , 000 , 52 , 000 , and 22 , 000 . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Characterization of the transcription start site of the ACTH receptor gene : presence of an intronic sequence in the 5 ' flanking region . ^^^ Analysis of the ACTH receptor mRNA in human adrenal has revealed the presence of five transcripts ranging from 1 . 8 to 11 kilobases ( kb ) . ^^^ Characterization of the 5 ' untranslated regions ( UTRs ) of the ACTH receptor mRNA demonstrated the presence of one major initiation site of transcription 177 bp away from the ATG codon . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Only one class of ACTH receptor was detected , with Kd = 2 . 57 + / 0 . 35 10 10 ( 9 ) M and Bmax = 1 . 59 + / 0 . 06 pmol / mg protein in high responders and Kd = 1 . 68 + / 0 . 18 10 10 ( 9 ) M and Bmax = 1 . 17 + / 0 . 11 pmol / mg protein in low responders . 4 . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The regulation of ACTH receptor binding sites and mRNA by ACTH and angiotensin 2 ( A 2 ) was studied using cultured human adrenal fasciculata reticularis cells ( HAC ) . ^^^ These cells expressed two major ACTH receptor transcripts of 1 . 8 and 3 . 4 kb and three minor ones of 4 , 7 , and 11 kb . ^^^ At a maximal concentration of 10 ( 8 ) M , ACTH enhanced 21 and 4 fold the level of ACTH receptor mRNA and the number of receptors per cell , respectively . ^^^ Pretreatment of HAC with A 2 produced a dose dependent enhancement of ACTH receptor mRNA that was associated with an increase of both ACTH receptor number and responsiveness to this hormone . ^^^ The effects of ACTH together with A 2 on ACTH receptor mRNA were greater than those induced by each hormone alone . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The maximal stimulatory effect ( 60 70 % rise ) was obtained with a VIP concentration of 10 ( 8 ) M . [ 4 Cl D Phe 6 , Leu 17 ] VIP , a VIP receptor antagonist ( VIP A ) , and corticotropin inhibiting peptide ( CIP ) , an ACTH receptor antagonist ( both 10 ( 6 ) M ) , completely annulled VIP ( 10 ( 8 ) M ) evoked rises in basal ALDO and corticosterone secretions . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Mutations of the ACTH receptor gene are only one cause of familial glucocorticoid deficiency . ^^^ Defects in the ACTH receptor have been suggested as a possible cause , and we have previously reported a point mutation in this gene in a family with FGD . ^^^ Investigation of seven additional families has revealed a number of novel mutations in the ACTH receptor in some , but a normal gene in others suggesting that the aetiology of FGD may be heterogeneous . ^^^ Using a highly polymorphic CA repeat marker ( D18S40 ) closely linked to the ACTH receptor locus , we are now able to confirm that some cases of FGD result from defects at another locus . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We investigated the DNA base sequence in a family with this condition by polymerase chain reaction amplification of DNA with pairs of primers that span the ACTH receptor domain . ^^^ The affected male proband showed a single base mutation , ser 74 > ile , in the sequence coding for the second transmembrane domain of the ACTH receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The cDNA and gene of the human ACTH receptor were recently cloned . ^^^ We hypothesized that the ACTH receptor gene might be defective in IGD . ^^^ We conclude that IGD in this family appears to be due to defects of the ACTH receptor gene . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Five Japanese patients with ACTH unresponsiveness were examined as to whether they have mutations in the putative ACTH receptor . ^^^ The coding region of the ACTH receptor gene was amplified by polymerase chain reaction and directly sequenced on both strands , however , no point mutation was found in any of the five patients , suggesting that familial glucocorticoid deficiency , caused by the mutated ACTH receptor , may be rare . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We isolated five independent cDNAs of nearly 3000 bp for the bovine ACTH receptor by screening adrenal cortex cDNA libraries with a PCR cloned cDNA fragment . ^^^ The deduced receptor sequence includes 297 residues ( M ( r ) = 33 , 258 ) with 81 % identity with the human ACTH receptor , and shows seven hydrophobic transmembrane domains . ^^^ Thus , the involvement of protein kinase A and C pathways in ACTH action may be mediated in part by phosphorylation of the ACTH receptor at these motifs . ^^^ The 3 ' untranslated region of the bovine cDNA is > 2000 bp and includes two inverse repeats giving an extensive and strong secondary structure to the ACTH receptor RNA . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
When BAC were incubated with [ 125I ] ACTH in the presence of 100 microM phenylarsine oxide at 20 degrees C , a condition which prevents the internalization of the ACTH receptor complex , the bulk of the radioactivity was present in the 43 , 000 band . ^^^ These results indicate that the ACTH receptor present at the cell surface is a macromolecule of 43 , 000 , and suggest that the 154 , 000 form probably represents association of the ACTH receptor complex to another macromolecule . ^^^ The 154 , 000 protein would be formed during or after internalization of the ACTH receptor complex . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Our results suggest that Addison ' s disease is not caused by circulating antibodies to the ACTH receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In addition to their antimicrobial and cytotoxic properties , some defensins act as opsonins , while others inhibit protein kinase C , bind specifically to the ACTH receptor and block steroidogenesis or act as selective chemoattractants for monocytes . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Functional characterization of the cloned human ACTH receptor : impaired responsiveness of a mutant receptor in familial glucocorticoid deficiency . ^^^ The putative ACTH receptor gene has been identified on the basis of its tissue specific expression , structure , and limited expression data . ^^^ The S74I mutant ACTH receptor gene that associates with the syndrome of familial glucocorticoid deficiency had an EC 50 of 67 10 10 ( 9 ) M . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The MC 2 receptor exhibits properties similar to the ACTH receptor characterized in adrenocortical cells , coupling to activation of adenylyl cyclase with an EC 50 of approximately 1 nM . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Therefore , in the present study we determined the levels of ACTH receptor messenger RNA ( mRNA ) and correlated ACTH receptor expression with appearance of the mRNA for delta 5 3beta hydroxysteroid dehydrogenase / isomerase ( 3betaHSD ) , the enzyme protein that signals functional maturation of the definitive cortical zone in the baboon fetal adrenal . ^^^ A baboon ACTH receptor complementary DNA was cloned and hybridized with polyadenylated RNA isolated from baboon ( Papio anubis ) fetal adrenals obtained in early ( days 58 64 ; RNA from seven baboon fetuses pooled to yield three samples ) , mid ( days 99 103 ; RNA from five baboons pooled to yield four samples ) , and late ( days 165 168 ; RNA of four individual baboon fetuses ) gestation ( term = 184 days ) . ^^^ Expression of the primary 3 . 4 kilobase ACTH receptor mRNA transcript , determined by Northern blot and expressed as a ratio of beta actin mRNA , was minimal early in gestation ( mean + / SE , 0 . 11 + / 0 . 05 arbitrary densitometric units ) . ^^^ However , fetal adrenal ACTH receptor mRNA levels increased ( P < 0 . 001 , by ANOVA ) approximately 13 fold to 1 . 41 + / 0 . 16 at midgestation , then declined by 70 % ( P < 0 . 001 ) to 0 . 41 + / 0 . 10 in late gestation . ^^^ To determine whether the decrease in ACTH receptor expression by the fetal adrenal in the second half of pregnancy reflected programmed cell death , the integrity of genomic DNA was assessed by 32P labeled DNA gel electrophoresis and in situ DNA end labeling . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Responsiveness of adrenal cortical cells to ACTH is dependent on the extent of ACTH receptor expression . ^^^ Therefore , we examined the localization and regulation of ACTH receptor expression in the midgestation ( 16 24 weeks ) human fetal adrenal cortex . ^^^ In situ hybridization analysis was used to localize messenger RNA ( mRNA ) encoding the ACTH receptor in sections of human fetal adrenal glands . ^^^ Messenger RNA encoding the ACTH receptor was localized in cells from all cortical zones ; abundance was higher in definitive zone than in fetal zone cells and was least abundant in the more central portions of the cortex . ^^^ Regulation of ACTH receptor expression was studied using Northern blot analysis of total RNA extracted from primary cultures of fetal and definitive zone cells . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The defects in the ACTH receptor causing IGD help illuminate the mechanisms of ligand binding and signal transduction by this receptor . ^^^ Identification of the molecular defect ( s ) responsible for IGD cases with a normal ACTH receptor structural gene and for the triple A syndrome remains a challenge , which will hopefully eventually provide further insight into the mechanisms of adrenocortical function . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The cloned mouse ACTH receptor was expressed in stably transfected human HeLa cells that lack an endogenous melanocortin receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Localization of ACTH receptor mRNA by in situ hybridization in mouse adrenal gland . ^^^ This action is presumed to be mediated by the ACTH receptor and is functionally connected with the hypothalamus pituitary adrenal axis . ^^^ To gain information concerning the distribution of the ACTH receptor in this axis , we examined mRNA for the ACTH receptor in the adrenal gland , pituitary and hypothalamus of the mouse , by using in situ hybridization . ^^^ The specific hybridization signal for ACTH receptor mRNA was uniformly distributed in the Y 1 cells , although the level of expression was low . ^^^ The adrenal cortex showed a strong signal for the ACTH receptor mRNA in both the zona fasciculata and the zona glomerulosa , sites that are involved in the mediation of the action of ACTH on the synthesis and release of glucocorticoids and aldosterone . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Recent cloning of the human ACTH receptor gene has enabled us to study this gene in patients with glucocorticoid deficiency . ^^^ By using the PCR to amplify the coding sequence of the ACTH receptor gene , we identified three mutations in two unrelated patients . ^^^ Normal and mutant ACTH receptor genes were expressed in the M 3 cell line , and intracellular cAMP production in response to ACTH was measured . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH receptor , CYP11A1 , CYP 17 and CYP21A2 genes are expressed in skin . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH and IGF 1 increased c fos and jun B mRNA levels early with later increases in the levels of mRNA for the ACTH receptor and the three steroidogenic enzymes , and enhanced steroidogenic responses to both ACTH and Ang 2 . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The results suggest that beta lipotropin stimulates steroidogenesis by acting on the conversion of cholesterol to pregnenolone and that its effects are not mediated via an opioid receptor but may be mediated via an ACTH receptor . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Germline loss of function mutations in rhodopsin , cone opsins , the V 2 vasopressin receptor , ACTH receptor , and calcium sensing receptor are responsible for retinitis pigmentosa , color blindness , nephrogenic diabetes insipidus , familial ACTH resistance , and familial hypocalciuric hypercalcemia , respectively . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Mutations of ACTH receptor gene and familial syndrome of glucocorticoid deficiency ] . ^^^ Recent cloning of the ACTH receptor allowed to study this receptor in this particular syndrome . ^^^ The mutant receptors were expressed in vitro in transfected M 3 cells ( S 91 Cloudman cells ) which represents a working expression system to express the ACTH receptor . ^^^ The EC 50 values were estimated ( C251F : 3 . 5 + / 0 . 9 10 10 ( 9 ) M , D107N : 3 . 0 + / 0 . 9 10 10 ( 9 ) M , G217fs : 4 . 8 + / 0 . 9 10 10 ( 9 ) M ) and comparison with the value obtained for the wild type ACTH receptor ( 5 . 1 + / 0 . 9 10 10 ( 10 ) M ) indicates a clear 6 to 9 shift to the right due to an impaired function of these mutant receptors . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In cells treated with IGF 1 or 2 , the messenger ribonucleic acid ( mRNA ) levels of cytochrome P 450 17 alpha hydroxylase and of 3 beta hydroxysteroid dehydrogenase were increased , and the abundance of ACTH receptor mRNA was also slightly enhanced , but the mRNA of cytochrome P 450 cholesterol side chain cleavage enzyme was unchanged . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
As a step for analysis of the transcriptional regulation of the adrenocorticotropin ( ACTH ) receptor gene , 1 have made an attempt to obtain a full length cDNA and determined the genomic organization of the mouse ACTH receptor . ^^^ By comparison of the 374bp sequence with the 1 . 8kb genomic sequence within the phage clone , lambda mCTR 8 , containing the mouse ACTH receptor coding region as described previously , a 95bp sequence of the 5 ' RACE generated cDNA was found to locate from the position of 1 to 95 from the ATG , and a 113bp sequence of the 5 ' RACE generated cDNA was found in the genomic sequence approximately 1 . 6kb upstream of the ATG . ^^^ The 3 ' non coding region of the mouse ACTH receptor cDNA obtained by 3 ' RACE method was contiguous to the coding region by comparing it with the 1 . 4kb genomic sequence downstream of the ATG . ^^^ Taken together , the mouse ACTH receptor gene consists of at least 4 exons and three of the exons encoded 5 ' untranslated sequences . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We demonstrate that the resistance of these mutants to ACTH results from the failure to express ACTH receptor transcripts . ^^^ Two spontaneous Y 1 mutants , Y 6 and OS 3 , previously characterized as ACTH resistant clones that failed to accumulate ACTH receptor transcripts , were shown to be forskolin resistant and to contain less Gs alpha in membrane fractions , indicating that forskolin resistance , failure to express the ACTH receptor , and the consequent reduction in Gs alpha are closely linked . ^^^ Expression of the human ACTH receptor in Y 6 and OS 3 cells restored ACTH responsive adenylyl cyclase activity and increased the level of Gs alpha , but did not otherwise reverse the forskolin resistant phenotype . ^^^ Together , these results demonstrate that mutations to forskolin resistance have downstream consequences that result in the loss of ACTH receptor expression and the consequent reduction in levels of membrane associated G alpha subunits . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Expression of the mouse ACTH receptor gene and characterisation of its promoter . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We have proposed , therefore , that there is a selective decrease in ACTH receptor expression and thus tropic responsivity to ACTH within the fetal zone in the second half of primate pregnancy . ^^^ ACTH receptor messenger RNA ( mRNA ) levels , determined by in situ hybridization , in the fetal zone of the baboon fetal adrenal were approximately 2 fold greater ( P < 0 . 05 ) at mid ( i . e . day 100 ) than at late ( i . e . day 170 ) gestation and 3 fold greater ( P < 0 . 01 ) in the definitive zone than in the fetal zone in late gestation ( term = 184 days ) . ^^^ Both ACTH receptor and low density lipoprotein receptor mRNA levels , determined by Northern blot in the whole fetal adrenal , also decreased ( P < 0 . 001 ) by approximately 50 % , whereas the mRNA levels for the definitive zone specific delta 5 3beta hydroxysteroid dehydrogenase / isomerase ( 3beta HSD ) enzyme required for cortisol biosynthesis increased over 13 fold ( P < 0 . 001 ) between mid and late gestation . ^^^ We conclude that the decrease in ACTH receptor mRNA expression and ACTH stimulable dehydroepiandrosterone formation in the second half of gestation reflect a decline in functional capacity of the fetal zone , whereas the increase in 3beta HSD mRNA expression and cortisol production results from the ACTH receptor mediated development and enhanced functional capacity of the definitive zone . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Characterization of the human ACTH receptor gene and in vitro expression . ^^^ The coding sequence of the human ACTH receptor , cloned in 1992 , contains no intron , but the presence of one intron ( of about 18 kb ) separating the coding exon from an upstream exon has been demonstrated . ^^^ To functionally characterize the human ACTH receptor , we have prepared cells stably transfected with either the normal receptor or a mutant receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
This study shows that chronic stress leads to a ) inhibition of mineralocorticoid secretion due to inhibition of the late biosynthetic pathway , and b ) increased circulating glucocorticoids due to increased ACTH receptor activity , expression and activity of the early pathway , and decreased glucocorticoid clearance . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Genomic structure and promoter characterization of the human ACTH receptor gene . ^^^ One kb of the 5 ' flanking region of the human ACTH receptor gene was isolated and partially characterized . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We examined the effects of recombinant human IGF 2 and the closely related peptide , IGF 1 , on 1 ) basal and agonist stimulated [ ACTH ( 1 24 ) , forskolin , or 8 bromo cAMP ] cortisol and DHEA S production , 2 ) basal and ACTH stimulated steady state abundance of messenger ribonucleic acids ( mRNAs ) encoding the steroidogenic enzymes cytochrome P 450 side chain cleavage ( P450scc ) and cytochrome P 450 17alpha hydroxylase / 17 , 20 lyase ( P450c17 ) , and 3 ) basal and ACTH stimulated steady state abundance of mRNA encoding the ACTH receptor . ^^^ Neither IGF 1 nor IGF 2 affected basal or ACTH stimulated abundance of mRNA encoding the ACTH receptor , suggesting that the increase in ACTH responsiveness was not mediated by an increase in ACTH binding capacity . ^^^ Taken together , these data indicate that activation of the type 1 IGF receptor increases ACTH responsiveness in fetal zone cells by modulating ACTH signal transduction at some point distal to ACTH receptor activation . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The ACTH receptor is the shortest G protein coupled receptor to date and consists of 297 residues with two putative glycosylation sites at the extracellular N terminus . ^^^ In vitro studies have demonstrated upregulation of the ACTH receptor by its own ligand and by angiotensin 2 . ^^^ Inactivating mutations of the ACTH receptor lead to the familial glucocorticoid deficiency ( FGD ) syndrome , a rare recessive autosomal disorder characterized by degeneration of the zona fasciculata / reticularis and unresponsiveness to exogenous ACTH . ^^^ Interestingly , ACTH receptor mutations are not present in all patients with FGD and also not in the closely related `` triple A ' syndrome indicating that other mechanisms of ACTH resistance are still to be elucidated . ^^^ Despite an extensive search , no activating ACTH receptor mutations have been found in adrenal tumors , excluding the ACTH receptor as a relevant oncogene for adrenal tumorigenesis . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH receptor ] . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Stable expression of normal and mutant human ACTH receptor : study of ACTH binding and coupling to adenylate cyclase . ^^^ Point mutations of the human ACTH receptor have been reported in some patients with a familial glucocorticoid deficiency syndrome . ^^^ We have developed a stable expression model in order to characterize the human ACTH receptor by binding studies and functional coupling to adenylate cyclase . ^^^ The EC 50 for ACTH were 2 . 9 + / 0 . 2 10 10 ( 10 ) M and 2 . 4 + / 0 . 8 10 10 ( 10 ) M , respectively , for two different clones stably expressing the normal human ACTH receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In 6 , mutations , in the coding region of the ACTH receptor are the cause of their ACTH resistance . ^^^ MEASUREMENTS : Physical examination , basal serum cortisol , basal plasma ACTH , serum cortisol after stimulation with 250 micrograms ACTH ( 1 24 ) , plasma dehydroepiandrosterone sulphate ( DHEAS ) and plasma androstenedione ( A 4 ) , total urinary androgen excretion and single stranded sequencing of the coding region of the ACTH receptor . ^^^ The lack of adrenarche was independent of the presence of a mutation within the ACTH receptor and of the severity of glucocorticoid deficiency . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The present study was designed to determine whether the induction of definitive zone ACTH receptor messenger RNA ( mRNA ) levels and components of the steroidogenic pathway known to be expressed specifically in the definitive zone , e . g . the 3beta HSD enzyme , are dependent upon fetal pituitary ACTH . ^^^ Associated with this decline in pituitary POMC , levels of the major 3 . 4 kb mRNA transcript for the ACTH receptor expressed as a ratio of beta actin were approximately 80 % lower ( P < 0 . 05 ) in fetal adrenals of betamethasone treated baboons ( 0 . 12 + / 0 . 02 ) than in untreated controls ( 0 . 84 + / 0 . 05 ) . ^^^ In situ hybridization indicated that ACTH receptor mRNA expression in the definitive zone exceeded that in the fetal zone and was reduced by betamethasone . ^^^ Associated with the decrease in ACTH receptor expression , fetal adrenal weight was suppressed ( P < 0 . 05 ) by 50 % and reflected a marked reduction ( P < 0 . 05 ) in the size of the cells of the definitive and fetal zones . ^^^ These findings indicate that treatment of the baboon fetus with betamethasone in late gestation suppressed fetal pituitary POMC mRNA expression and ACTH receptor mRNA levels in the fetal adrenal gland , as well as the hypertrophy and ACTH receptor mRNA and 3beta HSD mRNA / protein levels in the cells comprising the newly emerging definitive zone . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Among these , the adrenal ACTH receptor ( MC 2 R ) is selectively activated by ACTH . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
A number of mutations in the ACTH receptor have been demonstrated in patients with this disorder which are likely to lead to loss of receptor function and thus would account for the syndrome . ^^^ Several patients , however , do not have mutations in the ACTH receptor gene coding region , and it can be demonstrated by segregation analysis that another distant gene must account for the disease in some of these cases . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Ovine adrenocortical cells expressed one major ACTH receptor transcript of 3 . 6 kb and three minor ones of 4 . 2 , 1 . 8 and 1 . 3 kb . ^^^ Testosterone did not modify , while high concentrations of 17 beta estradiol decreased , ACTH receptor mRNA levels . ^^^ Treatment of cells with aminoglutethimide ( an inhibitor of steroidogenesis ) resulted in a dose dependent decrease in ACTH receptor mRNA levels , which was prevented by concomitant treatment with dexamethasone . ^^^ Treatment with ACTH also increased ACTH receptor mRNA levels more than twofold . ^^^ Neither dexamethasone nor ACTH modified ACTH receptor mRNA half lives . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Corticosterone response to BrdU was partially reversed by the ACTH receptor antagonist corticotropin inhibiting peptide ( CIP ) , and aldosterone response by the arginine vasopressin ( AVP ) V 1 receptor antagonist [ amino Pen 1 , Val 4 , D Arg 8 ] vasopressin ( AVP A ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In adrenocortical cells , the levels of expression of the Gs protein and ACTH receptor are decreased when the cells are deprived of ACTH and angiotensin 2 ( ANG 2 ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In the present study , therefore , baboons were treated at midgestation with betamethasone to determine the effect of fetal pituitary ACTH on fetal adrenal growth , development , and ACTH receptor and P 450 enzyme messenger ribonucleic acid ( mRNA ) levels . ^^^ Moreover , there was approximately a 95 % decrease ( P < 0 . 01 ) in fetal adrenal expression of ACTH receptor , P 450 cholesterol side chain cleavage , and P 450 17alpha hydroxylase 17 / 20 lyase mRNA levels after betamethasone administration . ^^^ We conclude that fetal pituitary ACTH is necessary for the growth and development of fetal and definitive cortical zones and the marked coordinated increase in ACTH receptor and maintenance of P 450 cholesterol side chain cleavage / P 450 17alpha hydroxylase 17 / 20 lyase expression in the baboon fetal adrenal gland during the first half of gestation . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In situ localization of ACTH receptor like mRNA in molluscan and human immunocytes . ^^^ These findings suggest that the ACTH receptor gene has been highly conserved during evolution . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH receptor mutation in a girl with familial glucocorticoid deficiency . ^^^ This mutation creates a new restriction enzyme site in the ACTH receptor gene , allowing accurate characterisation of the mutation without DNA sequencing . ^^^ Interestingly , she has a tall stature , a clinical finding reported in several children who have ACTH insufficiency and mutations of the ACTH receptor gene . ^^^ We suggest that mutation analysis of the ACTH receptor gene be considered in children with clinical features of FGD and tall stature . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The selective ACTH receptor antagonist corticotropin inhibiting peptide ( 10 [ 6 ] M ) annulled corticosterone response to 10 ( 9 ) M ACTH , but not to 10 ( 7 ) M PP . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Human ACTH hypersensitivity syndrome associated with abnormalities of the ACTH receptor gene . ^^^ OBJECTIVE : Activating mutations of the ACTH receptor have not been previously described . ^^^ We also examined biological activity of her circulating blood ACTH using bovine adrenocortical cell suspensions and ACTH receptor gene structure by Northern blotting analysis . ^^^ The ACTH receptor coding region was amplified by polymerase chain reaction using the leucocyte genomic DNA . ^^^ There were two base mutations ; cysteine 21 > arginine and serine 247 > glycine in the sequences coding for the first extramembranous N terminal domain and the third extramembranous loop of the ACTH receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The orphan nuclear receptor steroidogenic factor 1 ( SF 1 ) is involved in the transcriptional regulation of all the steroid hydroxylase genes , and also regulates the transcription of the genes for Mllerian Inhibitory substance ( MIS ) , alpha subunit of glycoprotein hormone , LHbeta , oxytocin , GnRH receptor , ACTH receptor , prolactin receptor , DAX 1 , and steroidogenic acute regulatory protein . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In summary , adrenal cells treated with ACTH results in a significant increase in the ratio of B / A in the ZF owing a noncompetitive inhibition of the 11 beta HSD 2 via the ACTH receptor . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Vasoactive intestinal peptide stimulates rat adrenal glucocorticoid secretion , through an ACTH receptor dependent activation of the adenylate cyclase signaling pathway . ^^^ A VIP receptor antagonist and the ACTH receptor antagonist corticotropin inhibiting peptide annulled both adrenocortical cell responses to VIP , while the protein kinase ( PKA ) inhibitor H 89 blocked only corticosterone response . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The ACTH receptor antagonist corticotropin inhibiting peptide ( 10 ( 6 ) M ) blocked corticosterone response of dispersed cells to 10 ( 9 ) M ACTH but not to 10 ( 7 ) M galanin ; conversely , the specific protein kinase A inhibitor H 89 ( 10 ( 5 ) M ) annulled the secretory response to both ACTH and galanin . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Constitutive activation of the ACTH receptor G protein cAMP signal cascade does not play a role in adrenal tumor formation . ^^^ Conversely , deletions of the ACTH receptor gene have been recently found in undifferentiated adenomas and in aggressive adrenocortical carcinomas . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH receptor , ACTH receptor anomaly , and familial glucocorticoid deficiency ] . ^^^ After the cloning of ACTH receptor or melanocortin 2 receptor ( MC 2R ) cDNA , several kinds of mutations in the receptor genes have been reported . ^^^ However , the apparently normal ACTH receptor gene in some affected children suggests that the etiology of FGD is heterogeneous . ^^^ In this short review , we describe the recent advances in the molecular biology of ACTH receptor genes , its post receptor signal transduction in the adrenocortical cells , and the molecular genetics of the FGD and a related syndrome , Allgrove syndrome . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Low levels of ACTH receptor messenger RNA were also detectable in the tumor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
As ACTH stimulates the secretion of both AAs and F , it is possible that the discordant relationship of these hormones in MMD patients results from a defect of adrenocortical ACTH receptor function or postreceptor signaling or subsequent biochemical events . ^^^ Furthermore , the molecular abnormality seen in MMD patients may suggest that the mechanism underlying the frequently observed discordances in the secretion of glucocorticoids and AAs ( e . g . adrenarche , surgical trauma , severe burns , or intermittent glucocorticoid administration ) are explainable solely via an alteration in the function of the ACTH receptor or postreceptor signaling . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Genetic heterogeneity of adrenocorticotropin ( ACTH ) resistance syndromes : identification of a novel mutation of the ACTH receptor gene in hereditary glucocorticoid deficiency . ^^^ We studied four kindreds with HGD and four kindreds with AS for abnormalities of the ACTH receptor ( ACTHR ) gene . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Since melanocortin receptors ( MCR ) are involved in some actions of agouti , we next determined whether agouti ' s antilipolytic effect is exerted through competitive antagonism of the ACTH receptor ( MCR 2 ) . ^^^ Forskolin ( 1 microM ) , an adenylate cyclase activator , induced a 48 % increase in lipolysis in human adipocytes ( P < 0 . 05 ) ; this effect was reversed by 100 nM agouti ( P < 005 ) , demonstrating that the antilipolytic effect of agouti is distal to the ACTH receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Several mutations in the coding exon of the ACTH receptor ( MC2R ) gene have been reported in cases of familial glucocorticoid deficiency or FGD . ^^^ Patients in these families present the typical clinical features of FGD , but no mutation was found in the coding exon of the ACTH receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
These mutants present complex phenotypes in which the activity of Gbeta / gamma is impaired , ACTH receptor gene expression is markedly diminished , and ACTH responsive adenylyl cyclase activity is lost . ^^^ In this study , we have tested the hypothesis that the impairment in Gbeta / gamma activity is responsible for the loss of ACTH receptor gene expression and ACTH responsive adenylyl cyclase activity . ^^^ Transfection of one of the mutant clones with expression vectors encoding either Gbeta 1 or Gbeta 2 together with Ggamma 2 increased ACTH receptor expression and restored ACTH responsive adenylyl cyclase activity . ^^^ These results thus support the hypothesis that the impairment in Gbeta / gamma activity is responsible for the loss of ACTH receptor expression . ^^^ A luciferase reporter plasmid driven by the proximal promoter region of the mouse ACTH receptor gene was expressed poorly in the mutants compared with parental Y 1 cells , suggesting that the Gbeta / gamma defect compromised transcriptional activity at the proximal promoter region of the ACTH receptor gene . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
They also stress that this side effect of CIP must be taken into account in interpreting the results of investigations on the adrenal cortex , where CIP has been employed as an ACTH receptor antagonist . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
However , a specific mechanism which couples ACTH receptor activation to increased intracellular calcium concentration in the adrenal cortical cell has not been elucidated . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
It is expressed in the adrenal cortex and is hence considered to be the ACTH receptor . ^^^ A DNA fragment , was obtained using primers based on the bovine ACTH receptor ( MC 2 R ) sequence . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The glucocorticoid secretagogue effect of 10 ( 8 ) M PP was blocked by the protein kinase A ( PKA ) unhibitor H 89 , but not by the ACTH receptor antagonist corticotropin inhibiting peptide ( CIP ) Autoradiography showed the presence of [ 125I ] PP binding sites in the inner zones of rat and human adrenal cortex , which were not displaced by NPY , PYY , ACTH or CIP . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
VIP seems to act through the VIP and / or PACAP receptor while PHI acts , directly or by sensitivity increase , through the ACTH receptor . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Low levels of ACTH receptor mRNA were also detectable in the tumor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In the present study , we characterized two new SF 1 binding sites , SF 209 and SF 98 , in the promoter of the human ACTH receptor ( hACTH R ) gene . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Molecular biology showed a composite heterozygotism for the ACTH receptor gene . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Two of these 3 patients were studied by immunohistochemistry of steroidogenic enzymes and for the gene expression of ACTH receptor by Northern blot analysis . ^^^ ACTH receptor messenger RNA was not detected in virilizing tumor tissues , whereas it was expressed in attached adrenal tissues . ^^^ CONCLUSIONS : The lack of response to ACTH is the result of a deficiency of ACTH receptor expression in the virilizing tumor cells . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Total RNA was isolated from the pituitary and adrenal glands to evaluate gene expression for mRNA specific for pro opiomelanocortin ( POMC ) and for the ACTH receptor . ^^^ Expression of ACTH receptor mRNA tended to be greater in C section pigs at birth ( P < . 063 ) and at 2 wk of age ( P < . 016 ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We have shown that ACTH receptor mRNA expression and steroidogenesis were increased in the transitional zone and decreased in the fetal zone of the baboon fetal adrenal in the second half of gestation . ^^^ Thus , we proposed that there is a divergence in ACTH receptor mediated zone specific steroidogenesis within the fetal adrenal during mid to late gestation . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Several missense mutations of the ACTH receptor ( MC 2 R ) gene have been associated with the autosomal recessive syndrome of familial glucocorticoid deficiency . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Autoradiography evidenced abundant [ 125I ] GIP binding sites exclusively in the inner adrenocortical layers , and the computer assisted densitometric analysis of autoradiograms demonstrated that binding was displaced by cold GIP , but not by either ACTH or the selective ACTH receptor antagonist corticotropin inhibiting peptide ( CIP ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Linkage analysis , using specific polymorphic markers , excluded the involvement of the ACTH receptor but not thyrotropin receptor ( TSHR ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
These results suggest the lymphocyte ACTH receptor is the Melanocortin 5 receptor and the receptor is internalized by endocytosis to deliver ligand to the lysosome . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The ACTH receptor antagonist corticotropin inhibiting peptide ( 10 ( 6 ) M ) annulled corticosterone response of ZF / R cells to ACTH ( 10 ( 9 ) M ) , but not to orexins ( 10 ( 8 ) M ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH receptor gene analysis revealed no mutations in the ACTH receptor coding region . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The response of the cultured theca cells was more acute than that of the adrenocortical cells , possibly reflecting the propensity of the LH receptor to desensitize rapidly , unlike the ACTH receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The receptor MC 2 ( ACTH receptor ) almost exclusively expressed in the adrenal cortex whereas MC 5 R is expressed in several organs including the adrenal cortex . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In FGD , several missense mutations within the coding region of the ACTH receptor ( MC 2 R ) have been identified in some , but not all patients , and segregation analyses and functional studies in a Y 6 cell expression system confirmed that these mutations cause the disease . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Isolated glucocorticoid deficiency and ACTH receptor mutations . ^^^ The etiological involvement of the ACTH receptor gene in isolated glucocorticoid deficiency has been recently established in many , but not all , affected families . ^^^ Several naturally occurring mutations of the ACTH receptor gene have been identified to date and have helped illuminate the mechanisms of ligand binding and signal transduction by this receptor . ^^^ Discovery of the molecular defect ( s ) responsible for isolated glucocorticoid deficiency in cases with a normal ACTH receptor gene coding region and for the triple A syndrome ( adrenal insufficiency , alacrima , achalasia ) will hopefully provide further insight into the mechanisms of adrenocortical function and will increase the prospect of new therapeutic approaches . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Here we report a 3 yr old girl with isosexual pseudoprecocious puberty due to an ovarian steroid tumor whose adrenal cell origin was determined by the presence of messenger ribonucleic acid ( mRNA ) of adrenal specific steroidogenic P 450 enzymes ( P450c11 and P450c21 ) and ACTH receptor ( ACTHR ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Regulation by adrenocorticotropin ( ACTH ) , angiotensin 2 , transforming growth factor beta , and insulin like growth factor 1 of bovine adrenal cell steroidogenic capacity and expression of ACTH receptor , steroidogenic acute regulatory protein , cytochrome P450c17 , and 3beta hydroxysteroid dehydrogenase . ^^^ The purpose of this study was to evaluate the time course effect of a 36 h treatment with ACTH ( 10 ( 8 ) M ) , transforming growth factor beta 1 ( TGFbeta 1 ; 10 ( 10 ) M ) , angiotensin 2 ( AngII ; 10 ( 7 ) M ) , and insulin like growth factor 1 ( IGF 1 ; 10 ( 8 ) M ) on the steroidogenic capacity of bovine adrenocortical cells ( BAC ) and on messenger RNA ( mRNA ) levels of ACTH receptor , cytochrome P450c17 , 3beta hydroxysteroid dehydrogenase ( 3betaHSD ) , steroidogenic acute regulatory protein ( StAR ) , and StAR protein . ^^^ ACTH , IGF 1 , and AngII increased ACTH receptor mRNA , but the opposite was observed after TGFbeta 1 treatment . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Novel mutations of the ACTH receptor gene in a female adult patient with adrenal unresponsiveness to ACTH . ^^^ Direct sequencing and allele specific amplification revealed two novel mutations in the ACTH receptor gene . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
PATIENTS AND METHODS : Five patients with a clinical diagnosis of FGD are described in whom the disorder resulted from a variety of novel or previously described missense or nonsense mutations of the ACTH receptor ( MC 2 R ) . ^^^ CONCLUSIONS : These findings indicate that ACTH resistance resulting from a defective ACTH receptor may be associated with abnormalities of cartilage and / or bone growth independently of the GH IGF 1 axis , but probably dependent on ACTH actions through other melanocortin receptors . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The results suggest that there is a reduction in adrenal ACTH receptor number or affinity , with a high basal production rate in vivo maintaining the elevated plasma cortisol levels . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
While the mechanisms of tumorigenesis for adrenocortical neoplasms remain unknown , several genes , such as Gsalpha , ACTH receptor ( MC 2 R ) , p 53 , and p 16 tumor suppressor genes , are considered to be candidates for adrenocortical neoplasms . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In the present study , we show direct evidence that human aortic endothelial cells possess the ACTH receptor . 11beta Dehydrogenation , converting cortisol to its inactive metabolite , cortisone , mediated by vascular 11beta hydroxysteroid dehydrogenase type 2 is essential for the control of vascular tone , and the reduced activity may be relevant to the pathogenesis of hypertension . ^^^ We found that ACTH ( 1 24 ) dose dependently decreased the gene expression and enzyme activity of 11beta hydroxysteroid dehydrogenase type 2 in these cells , and the decrease was partially abolished by a selective ACTH receptor antagonist . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In FGD type 1 , ACTH receptor mutations have been described and are responsible for the loss of function of the receptor , leading to the ACTH unresponsiveness . ^^^ Patients with FGD type 2 show the same phenotype as in the previous syndrome but no mutation of the ACTH receptor has been reported in these cases . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Functional expression of the human ACTH receptor gene . ^^^ The ACTH receptor is the type 2 ( MC2R ) among the melanocortin receptor family and is expressed almost exclusively in the adrenal cortex . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Cells derived from the tumor of founder 1 ( ATC 1 ) were grown in presence of forskolin to maintain ACTH receptor expression and were tested for ACTH responsiveness by immunocychemistry and northern blot analyses . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
To further understand the relative roles of the pituitary gland and ACTH in the regulation of mRNAs encoding proteins that are essential for adrenal development , we investigated the effects of , first , an ACTH infusion and labour in intact fetuses and , secondly , the effect of an ACTH infusion to fetuses with and without a pituitary gland , on the relative abundance of the mRNA encoding for the ACTH receptor ( MC2R ) , steroidogenic factor 1 ( SF 1 ) , cholesterol side chain cleavage enzyme ( P 450 ( scc ) ) , 3beta hydroxysteroid dehydrogenase ( 3betaHSD ) and 17alpha hydroxylase ( P 450 ( C 17 ) ) in the fetal adrenal gland . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The data also demonstrate the expression of MC 5 R protein on rat lymphocytes , thus , supporting the hypothesis that MC 5 R is the ACTH receptor on lymphocytes . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH receptor expression , regulation and role in adrenocortial tumor formation . ^^^ The regulation of the ACTH receptor gene is unique in that it is up regulated by its own ligand , ACTH . ^^^ Ligand induced up regulation of ACTH receptor expression may be an important adaptive process directed towards optimizing adrenal responsiveness to ACTH in the context of physiological stress and the maintenance of metabolic homeostasis in which the adrenals play a pivotal role . ^^^ Since the cloning of the promoter region of the ACTH receptor , considerable progress in the understanding of the regulatory processes has been made . ^^^ The effects of ACTH on ACTH receptor expression is dependent on cAMP , probably mediated through AP 1 . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Mutations of the ACTH receptor gene in a new family with isolated glucocorticoid deficiency . ^^^ Mutations of the ACTH receptor gene have been reported in several families with IGD . ^^^ We have amplified and directly sequenced the entire intronless ACTH receptor gene in a new family with IGD . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The cortisol response to 10 ( 8 ) mol / L orexin A was unaffected by the ACTH receptor antagonist corticotropin inhibiting peptide , but was abolished by either SQ 22536 or the protein kinase A inhibitor H 89 . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
There is a progressive and concurrent increase of ACTH 1 39 and cortisol ( F ) in the circulation of fetal sheep during the last 15 20 days of pregnancy ( term , day 145 150 ) associated with increased expression of hypothalamic CRH pituitary POMC and adrenal ACTH receptor and steroidogenic enzymes , particularly P 450 C17 . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In the present study , we have examined the developmental pattern of ACTH receptor ( ACTH R ) expression during the latter half of pregnancy and in neonatal and adult life . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Constitutive activation of the ACTH receptor G protein cAMP signal cascade does not play a role in adrenal tumour formation . ^^^ Conversely , deletions of the ACTH receptor gene have recently been found in undifferentiated adenomas and in aggressive adrenocortical carcinomas , and , more recently , confirmed in a larger series of tumours . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The binding of 125I labeled [ Phe 2 , Nle 4 and Ala 24 ] ACTH ( 1 24 ) to two transformed clones of mammalian cells expressing the guinea pig ACTH receptor was also competitively inhibited by ASIF and BNP . ^^^ Overall , the findings clearly demonstrated that ASIF and BNP suppressed the adrenocortical function and inhibited ACTH for their antagonistic action against ACTH primarily at the ACTH receptor site . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Familial glucocorticoid deficiency is one of these syndromes in which about half of all cases have inactivating mutations of the ACTH receptor . ^^^ The remaining patients with this syndrome have defects in one or more other as yet unidentified genes that are unlinked to the ACTH receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Angiotensin 2 type 1 receptor and ACTH receptor expression in human adrenocortical neoplasms . ^^^ We investigated the type 1 Ang 2 receptor expression in adrenocortical tissues to define its regulation in adrenocortical neoplasms and to compare its expression with that of the ACTH receptor ( ACTH R ) . ^^^ ACTH receptor mRNA followed a similar pattern ( CPA 178 + / 17 , APA 196 + / 30 , NFA 0 % , carcinomas 56 + / 11 % ) with a good correlation between Ang 2 type 1 receptor and ACTH R mRNA of r = 0 . 692 , P = 0 . 0019 . ^^^ CONCLUSIONS : Angiotensin 2 type 1 receptor and ACTH receptor expression seems to be correlated with the functional status of adrenocortical tumours , suggesting regulation by similar factors . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
OBJECTIVE : To examine whether inhibition of endogenous adrenocorticotropin ( ACTH ) secretion in patients with Cushing syndrome affects the expression of the ACTH receptor ( ACTH R ) gene in adrenocortical adenoma and attached atrophic normal gland . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The level of cholesterol side chain cleavage cytochrome P 450 mRNA in the salt inducible kinase overexpressing cells was markedly low compared with that in the parent , while the levels of Ad4BP / steroidogenic factor 1 , ACTH receptor , and steroidogenic acute regulatory protein mRNAs in the former were similar to those in the latter . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH receptor distribution and modulation among murine mononuclear leukocyte populations . ^^^ Murine mononuclear leukocytes express adrenocorticotropin ( ACTH ) receptors that were recognized by a monospecific antiserum to the ACTH receptor on Y 1 adrenal cells . ^^^ Helper T cells ( CD4+ T cells ) constituted the majority of ACTH receptor positive T lymphocytes . ^^^ The T lymphocyte mitogen , concanavalin A , interferon gamma , and ACTH enhanced ACTH receptor expression . ^^^ The differential distribution of ACTH receptor positive cells among specific leukocyte populations explains in part why differential cellular responses are observed and implies important regulatory functions for these receptors in the generation or regulation of immune responses . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In Crhr 1 / mice , intravenous ACTH administration failed to stimulate corticosterone secretion despite a significant upregulation of ACTH receptor mRNA levels in the adrenal cortex of these mutants . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In addition , ASIF and BNP 32 , which are the proven ACTH receptor antagonists , reduced the cortisol stimulatory effect of ACTH and VIP . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Unresponsiveness to ACTH may be due to a mutation in the ACTH receptor ; sometimes no mutation is found . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
These results led us to speculate that the overexpression of hDiminuto in the adenoma could be due to the abundant expression of ACTH receptor , as we previously described . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Familial glucocorticoid deficiency due to corticotropin ( ACTH ) resistance consists of two distinct genetic syndromes that are both inherited as autosomal recessive traits : isolated ACTH resistance ( iACTHR ) , which may be caused by inactivating mutations of the ACTH receptor ( the MC2R gene ) or mutations in an as yet unknown gene ( s ) , and Allgrove syndrome ( AS ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
To further characterize the carcinomas , telomerase activity and the expression of the ACTH receptor gene were determined . ^^^ Telomerase activity in the carcinomas resulted in levels significantly higher than in the adenomas , whereas the levels of ACTH receptor mRNA were lower in the carcinomas . ^^^ No correlation was found in the carcinomas between the levels of the ACTH receptor transcript and the loss of expression of CREB / inducible cAMP early repressor , suggesting that this alteration is not secondary to an upstream disregulation at the receptor level . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
It has been already excluded that activating mutations of the ACTH receptor or of G protein stimulator alpha sub units , affecting cAMP pathway , is involved in the tumorigenesis . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Protein levels of P450c21 and the ACTH receptor were increased in Dax 1 ( / Y ) mice and intermediate in SF 1 ( + / ) : Dax 1 ( / Y ) mice following chronic food deprivation . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Functional relationships between three novel homozygous mutations in the ACTH receptor gene and familial glucocorticoid deficiency . ^^^ Mutations of the ACTH receptor ( MC 2 R ) gene have been reported in some FGD cases , but only a few of them have been functionally studied . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The ACTH receptor ( MC2R ) is expressed predominantly in the adrenal cortex , but is one of five G protein coupled , seven transmembrane melanocortin receptors ( MCRs ) , all of which bind ACTH to some degree . ^^^ This assay provides excellent sensitivity in an easily assayed transient transfection system , providing a more rapid and efficient measurement of ACTH receptor activity . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Whilst periconceptional undernutrition ( R R and R C groups ) resulted in higher fetal plasma adrenocorticotrophic hormone ( ACTH ) at 135 146 d gestation , there was no change in the relative level of expression of the ACTH receptor ( MC2R ) , steroidogenic acute regulatory protein ( StAR ) or steroidogenic enzyme mRNAs in the fetal adrenal in late gestation . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
A naturally occurring ACTH receptor [ melanocortin 2 receptor ( MC2R ) ] mutation ( F278C ) has been identified in a subject with ACTH independent Cushing ' s syndrome . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Among these are the clinical syndromes resulting from defects in DAX 1 and SF 1 and the functional defects caused by mutations in the ACTH receptor and the StAR protein . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In neither patient were mutations found in the ACTH receptor gene . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH resistance in four mutant derivatives of a mouse adrenocortical tumor cell line results from a defect that reduces the activity of steroidogenic factor 1 ( SF 1 ) thereby preventing expression of the ACTH receptor and other SF 1 dependent genes . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Expression of ACTH receptor pathway genes in GIP dependent Cushing ' s syndrome ( CS ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Familial glucocorticoid deficiency due to the ACTH receptor gene mutations ] . ^^^ Recently , mutations in the ACTH receptor gene were identified in several families with FGD . ^^^ Interestingly and unexpectedly , the FGD patients with the ACTH receptor gene mutations were shown to be tall . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Although ACTH signaling through adenylyl cyclase and protein kinase A is important for normal adrenal cellular physiology , there is evidence to suggest that this pathway may inhibit the growth of adrenocortical tumors , and that inactivation of the ACTH receptor may promote tumor formation . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
While no differences in preadipocyte factor 1 , the presumed marker of primitive adrenocortical cells , were detectable in the adrenals of wt and SF 1 ( + / ) mice , an increase in the ACTH receptor as well as agouti related protein was observed only in wt animals but not in the SF 1 ( + / ) mice following uADX . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Direct sequencing of the genomic DNA of the patients failed to reveal mutations or other defects in the coding sequence of the ACTH receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We previously showed an ACTH receptor overexpression in APAs compared with the other adrenal tumors . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We investigated whether activating mutations in the ACTH receptor ( MC 2 R ) or G ( s alpha ) ( GNAS 1 ) genes might be involved in AIMAH genesis . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Finally , it has been suggested that certain neurotransmitters , particularly VIP , may interact with classical hormone receptors in the adrenal , notably the ACTH receptor . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Expression levels of ACTH receptor mRNA in adrenals increased with age in the female rat , but not in the male . ^^^ Castration enhanced the level of ACTH receptor mRNA to three fold of that in intact male rats at 14 days of age , but replacement treatment with testosterone in castrated male rats lowered the elevated levels . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Expression , desensitization , and internalization of the ACTH receptor ( MC2R ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
A polymorphic form of steroidogenic factor 1 associated with ACTH receptor deficiency in mouse adrenal cell mutants . ^^^ We have described a family of adrenocortical tumor cell mutants ( including clones OS 3 , Y 6 , and 10r9 ) that are resistant to ACTH because they fail to express the gene encoding the ACTH receptor ( MC2R ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The ACTH receptor [ melanocortin type 2 receptor ( Mc2r ) ] was identified within this fetal specific group . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH receptor mRNA expression was assessed using reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ ACTH receptor mRNA was present in mouse adipose tissue , but undetectable in human adipose tissue . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
TP 53 is involved in progression to carcinoma in a subset of patients and the frequency of ACTH receptor deletion needs to be more fully explored . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Daily administration of dexamethasone ( DEX ) ( 0 . 5 mg / 100 g body weight . d ) for 6 d in mice , decreased steroidogenic function of adrenal as shown by inhibition of the 36 kDa ACTH receptor protein expression , and decreased plasma corticosterone level [ control from 465 + / 35 ng / ml to 114 + / 18 ng / ml in DEX group ( P < 0 . 001 ) ] . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Simultaneously , there was an increase in the mRNAs of the ACTH receptor and of the steroid synthesizing enzymes in the fetal adrenal gland of the older , hypoxemic fetuses . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We also showed that the MC2R gene in Fugu codes for an ACTH receptor , which did not respond to alpha MSH . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Therefore , we quantitated ACTH receptor expression in the ovine adrenal cortex during development and after manipulations to better understand the regulation of the adrenal receptor in vivo . ^^^ ACTH receptor mRNA was quantitated by ribonuclease protection assay . ^^^ RESULTS : ACTH receptor mRNA level progressively increased in fetal life ; relative changes in receptor mRNA and binding were similar ( 3 . 0 fold and 2 . 4 fold , respectively ) . ^^^ Physiologic increases in fetal plasma cortisol decreased adrenal ACTH receptor mRNA concentration , and there was a strong ( r2=0 . 76 , P < . 002 ) linear relationship between fetal plasma ACTH concentration and receptor mRNA levels . ^^^ CONCLUSION : The data suggest that developmental increases in receptor expression are part of the maturation process in the fetal adrenal and that plasma ACTH concentration plays a major role in regulating ACTH receptor mRNA levels in vivo . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
We have , therefore , examined the expression and function of the ACTH receptor ( the melanocortin 2 receptor , MC 2 R ) in human and mouse primary islet tIssue and in the MIN 6 mouse insulinoma cell line . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Approximately 40 % of patients with FGD have an identifiable mutation in the ACTH receptor gene . ^^^ Patients with point mutations in the ACTH receptor gene are noted to be of tall stature . ^^^ Sequence analysis of the ACTH receptor gene showed compound heterozygosity , with two previously reported mutations : S74I and T159K . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Thus , for ACTH receptor binding and activation , the amino acid residues 15 18 are important for their side chains . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Similarly , in adrenal malignancies , significantly reduced levels of expression of the ACTH receptor gene were found . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH resistance results from a defect affecting transcription of the ACTH receptor and can be overcome by transfecting mutant cells with expression vectors encoding G beta / gamma . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Constitutive activation of the human ACTH receptor resulting from a synergistic interaction between two naturally occurring missense mutations in the MC2R gene . ^^^ Two mutations in the same allele of the ACTH receptor ( melanocortin 2 receptor , MC2R ) associated with clinical hypersensitivity to ACTH have been described in a single case report . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The ACTH receptor has a pivotal role in the regulation of adrenal cortisol secretion . ^^^ Here , we describe a polymorphism within the transcription initiation site of the ACTH receptor promoter altering the consensus sequence from CTC to CCC . ^^^ In conclusion , we describe an ACTH receptor promoter polymorphism that results in a lower promoter activity in vitro and is associated with a lower cortisol secretion to prolonged ACTH stimulation in vivo . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The role of the ACTH receptor in adrenal tumors : identification of a novel microsatellite marker . ^^^ In vivo , activation of the ACTH receptor ( ACTHR ) has a trophic effect on the adrenal cortex , while the effects on proliferation are still under discussion , especially since other POMC derived peptides have been characterized . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Transcripts of TSH receptor , GH receptor and ACTH receptor were detected in this cell line . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The authors believe that these two molecules competed with each other at the ACTH receptor and , thus , the bioactivity of ACTH 1 39 was masked and Cushing features were not manifested in the patient . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The whole pathway activated by ACTH to destabilize c Myc protein in Y 1 cells might comprise the following steps : ACTH receptor > cAMP / PKA > Akt deactivation > GSK 3 activity liberation > c Myc Thr 58 phosphorylation . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Castration enhanced the level of ACTH receptor mRNA to 3 fold of that in intact male rats at 14 days of age , but replacement treatment with testosterone in castrated male rats lowered the elevated levels . ^^^ These findings suggest that : 1 ) the hyporesponsiveness of adrenocorticosteroid in the stress hyporesponsive period of neonates might be dependent on the reduction of ACTH receptor mRNA , and 2 ) endocrine disrupting chemicals , with characters of androgens , estrogens or gonadotropin releasing hormones , might affect the responsiveness to ACTH and the ACTH receptor mRNA expression levels in adrenal cells of neonates . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Mutations in MRAP , encoding a new interacting partner of the ACTH receptor , cause familial glucocorticoid deficiency type 2 . ^^^ Mutations of the ACTH receptor ( melanocortin 2 receptor , MC2R ) account for approximately 25 % of cases of FGD . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Excessive growth was described previously in some patients with FGD , many of whom were shown to have mutations in the ACTH receptor gene . ^^^ We analyzed the ACTH receptor gene in three patients with FGD and discussed the causes of excessive growth in FGD . ^^^ No mutations were detected in the coding and promoter regions of the ACTH receptor gene of one female patient who had tall stature ( + 2 . 41S . ^^^ We speculate that the major causes of excessive growth in FGD are not only from ACTH receptor mutation , but also from the action of elevated plasma ACTH . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In addition , high concentrations of PCB 126 might sensitize the regulation of adrenocorticotropin ( ACTH ) on the adrenocortical cells by increasing ACTH receptor levels . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Brain , pituitary gland , and adrenal gland were obtained to determine the mRNA levels for corticotropin releasing hormone ( CRH ) , CRH receptor 1 ( CRHR 1 ) , pro opiomelanocortin ( POMC ) , ACTH receptor ( MC2R ) , c jun and c fos . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
As the primary messenger generated in response to ACTH receptor activation , cAMP acts at multiple sites to produce the full steroidogenic response that includes both rapid and delayed components . ^^^ In this way , ACTH receptor activation increases cAMP and Ca ( 2+ ) in the AZF cell , yielding the full steroidogenic response . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
On the molecular level , NCI h 295 cells expressed higher levels of ACTH receptor ( melanocortin receptor 2 ) mRNA upon treatment , whereas cyclin E mRNA was reduced , thus reflecting a shift toward an expression pattern found in less aggressive adrenocortical tumors in vivo . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Immunohistochemistry showed positive staining against chromogranin A in a histological specimen obtained from the right hand adrenal gland , while the left was negative ; the left hand adrenal gland stained positive against the ACTH receptor ( MC2R ) while the right was negative . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Real time PCR was used to quantify mRNA for steroidogenic acute regulatory protein , 17alpha hydroxylase ( CYP 17 ) , 21 hydroxylase ( CYP 21 ) , cholesterol side chain cleavage ( CYP11A1 ) , 3beta hydroxysteroid dehydrogenase type 2 ( HSD3B2 ) , and the ACTH receptor . ^^^ Adrenal mRNAs for CYP 17 , CYP11A1 , and the ACTH receptor were significantly reduced in LTH fetal sheep compared with levels shown in controls . ^^^ We conclude that expression of two key steroidogenic enzymes ( CYP 17 , CYP11A1 ) regulating cortisol biosynthesis and the ACTH receptor is lower in response to LTH . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
OBJECTIVES : Although several lines of evidence suggest that the overall effects of the ACTH receptor , melanocortin 2 receptor ( MC 2 R ) , mediated signal transduction on adrenocortical growth and tumorigenesis are anti proliferative , activation of MC 2 R induces mitogens like jun , fos , and myc and activates the MAPK pathway . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
More rarely , mutations in Gs protein ( gsp ) and the gene for ACTH receptor have been observed in ACTs . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Genetic influence of an ACTH receptor promoter polymorphism on adrenal androgen secretion . ^^^ Here we investigate the influence of an ACTH receptor promoter polymorphism affecting ACTH receptor gene transcription on ACTH dependent dehydroepiandrosterone ( DHEA ) secretion . ^^^ DESIGN : We recently reported a polymorphism within the transcription initiation site of the ACTH receptor gene promoter that alters the consensus sequence from CTC to CCC at 2 bp . ^^^ CONCLUSION : These data demonstrate that genetic variations within the ACTH receptor promoter result in decreased DHEA secretion . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Inactivating mutations of the ACTH receptor account for approximately 25 % of these cases . ^^^ The MRAP protein appears to function in the trafficking and cell surface expression of the ACTH receptor , and might indicate the existence of more widespread G protein coupled receptor trafficking mechanisms . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Expression of ACTH receptor pathway genes in glucose dependent insulinotrophic peptide ( GIP ) dependent Cushing ' s syndrome . ^^^ GIPR presumably acts , like the ACTH receptor ( ACTHR ) , through the Gs protein / cyclic AMP / protein kinase A ( PKA ) pathway to stimulate steroidogenesis . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH receptor , StAR and p450c17 mRNA levels were down regulated in adrenal tissue from UN ewes . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The aim of this study was to investigate the short term regulation of the ACTH receptor human ( h ) melanocortin receptor 2 ( MC2R ) by transfection of a c Myc tagged hMC2R in the M 3 cell line and assess its membrane expression by indirect immunofluorescence . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
CONTEXT : Mutations in MRAP , an interacting partner of the ACTH receptor , have been shown recently to cause familial glucocorticoid deficiency ( FGD ) in kindreds with confirmed FGD and no ACTH receptor mutations . ^^^ The DAX 1 , ACTH receptor ( MC2R ) , and MRAP genes were analyzed . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Adrenocorticotropic hormone receptor ( ACTHR ) is expressed predominantly in the adrenal glands , and its expression is upregulated by its own ligand , ACTH , via a cAMP dependent pathway . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The cloning of the melanocyte stimulating hormone ( MSH ) and adrenocorticotropic hormone ( ACTH ) receptors ( MC 1 R and MC 2 R , respectively ) recently has led to the identification of three additional melanocortin receptors , MC 3 R , MC 4 R , and MC 5 R . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The chicken MC 2 R mRNA is expressed in the adrenal and spleen , suggesting that the receptor mediates both endocrine and immunoregulatory functions of ACTH in the chicken . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
ACTH receptors exhibited a dual response since after 14 days of permanent stress MC 2 R showed a slight reduction while MC 5 R was still up regulated . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The ACTH and alpha MSH inhibitory effects on leptin secretion were mediated by activation of the MC 2 R and MC 5 R and were reversed by the MC R antagonists ACTH ( 11 24 ) and ACTH ( 7 38 ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
MC 1 R , found on melanocytes , is involved in pigmentation , while MC 2 R is the classic adrenocorticotropic ( ACTH ) receptor found on the adrenal cortex and adipocytes . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In adrenal fasciculata cells , the glucocorticoid secretion is under the control of ACTH , which binds specifically MC 2 R , the only functional melanocortin receptor described in these cells to date . ^^^ Nevertheless , using cultured bovine fasciculata adrenal cells , we report that Agrp has no antagonistic properties against ACTH at the level of MC 2 R . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Our data confirmed that Agrp is not an antagonist of ACTH at the level of MC 2 R and that its sustained effect on ACTH induced steroidogenesis did not involve its antagonistic properties at the level of MC 4 R . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
CRH , alpha MSH , and ACTH also modulate expression of their cognate receptors ( CRH R 1 , MC 1 R , MC 2 R ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
In normal physiology , the pituitary hormone corticotropin ( ACTH ) regulates the secretion of glucocorticoids via its G protein coupled receptor ( ACTHR ) , the product of the MC2R gene . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The adrenocorticotropic hormone ( ACTH ) acts on adrenocortical cells and promotes steroidogenesis by specific binding to the ACTH ( MC 2 ) receptor ( ACTHR ) . ^^^ To gain an insight into ACTH action on local steroidogenic organs , we examined the immunohistochemical expression of ACTHR in rat adrenal glands and placentas during the mid late gestation period . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Mutants isolated from the Y 1 mouse adrenocortical tumor cell line ( clones 10r 9 and 10r 6 ) are resistant to ACTH because they fail to express the melanocortin 2 receptor ( MC2R ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Using the mouse adrenocortical Y 1 cell line we demonstrate that ACTH effectively desensitizes the cAMP response of its own receptor , the melanocortin 2 receptor ( MC2R ) , in these cells with a maximal effect between 30 and 60 min . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Difficulty in expressing the adrenocorticotrophin ( ACTH ) receptor ( melanocortin 2 receptor ; MC2R ) after transfection of various MC2R expression vectors has been experienced by many researchers . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The physiological effects of the pituitary hormone , adrenocorticotropic hormone ( ACTH ) on the adrenal are mediated by the melanocortin 2 receptor ( MC2R ) , a G protein coupled receptor ( GPCR ) that signals via adenylate cyclase to elevate intracellular cyclic AMP ( cAMP ) levels . ^^^ The mode of internalization for the endogenous MC2R in Y 1 cells was determined using radiolabelled ACTH . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
Additionally , a systematic truncation study of the adrenocorticotropin hormone ( ACTH 1 24 ) has been performed and characterized at the cloned MC2R . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
With the exception of cyp21a and mc2r genes which were constitutively expressed , most of the genes above mentioned were induced in a time and dose dependent fashion in response to ACTH or PRL while DAX 1 was repressed . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
The present study addresses the regulation of cortisol release by ACTH and alpha MSH in common carp ( Cyprinus carpio ) and includes characterization of their receptors , namely , the melanocortin 2 and melanocortin 5 receptors ( MC2R and MC5R ) . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
These findings show the spatio temporal specific expression patterns of MC2R and MC5R in the mouse embryo and suggest that ACTH may be related to histogenesis and / or prenatal function of various tissues and organs via MC2R and / or MC5R . . ^^^
Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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Interacting proteins: Q01718 and P01189	Pubmed	SVM Score :0.0
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