| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.63255846 |
| Here , we provide evidence for two additional direct interactions between TRH and TRH R . 0.63255846^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.54706077 |
| These data are consistent with the idea that there are initial interactions between TRH and the residues of a putative entry channel of TRH R . 0.54706077^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We showed previously that the level of TRH receptor ( TRH R ) mRNA in rat pituitary GH 3 cells is down regulated by TRH . ^^^ Here , we study the mechanism of regulation of TRH R mRNA in a line of GH 3 cells that are stably transfected with mouse pituitary TRH R cDNA ( GH mTRHR 1 cells ) . ^^^ GH mTRHR 1 cells were found to have 2 . 4 times the number of TRH Rs and to stimulate a 2 . 5 fold greater increase in inositol phosphates in response to TRH than the parent cell line and to show TRH induced down regulation of TRH R number . ^^^ GH mTRHR 1 cells contained 26 + / 1 . 6 molecules of mouse TRH R mRNA / cell and 230 + / 31 molecules of mRNA for the neomycin resistance gene ( NEO ) with which it was cotransfected . ^^^ In GH mTRHR 1 cells , TRH caused a dose dependent transient decrease in mouse TRH R mRNA , with a nadir to 20 % of control levels after 6 h . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| In rat pituitary GH 3 cells , thyrotropin releasing hormone ( TRH ) down regulates TRH receptor ( TRH R ) mRNA ( Fujimoto , J . , Straub , R . ^^^ Here we show that TRH regulates RNase activity in GH 3 cells and that specific mRNA sequences are needed for in vivo regulation of TRH R mRNA by TRH . ^^^ This time course paralleled the effects of TRH on degradation of TRH R mRNA in vivo . ^^^ The regulated RNase activity was in a polysome free fraction of the lysates and was not specific for TRH R RNA . ^^^ A truncated form of TRH R RNA that was missing the entire 3 ' untranslated region ( TRHR R 5 ) was more stable than full length TRH R RNA ( TRHR WT ) . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We found previously that the level of endogenous TRH receptor ( TRH R ) mRNA in pituitary ( GH 3 ) cells and the level of mouse TRH R mRNA in GH 3 cells stably transfected with mouse pituitary TRH R cDNA are down regulated by TRH . ^^^ This down regulation is caused by TRH stimulation of TRH R mRNA degradation via a mechanism that appears to involve protein kinase C . ^^^ In this report we study regulation of TRH R mRNA in monkey kidney ( COS 1 ) cells transiently transfected with mouse pituitary TRH R cDNA . ^^^ In transfected COS 1 cells , TRH and phorbol 12 myristate 13 acetate ( PMA ) caused increases in the level of TRH R mRNA . ^^^ In contrast , TRH caused only a small transient increase in the level of the mRNA for the neomycin resistance gene , which was cotransfected with TRH R , and did not affect the level of the mRNA for glyceraldehyde phosphate dehydrogenase , an endogenous gene . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Thyrotropin releasing hormone , TRH ( < Glu His Proamide ) , and [ N tau Me His ] TRH ( MeTRH ) are present as neutral and positively charged forms at physiologic pH , and it was possible that they bind to the TRH receptor ( TRH R ) as charged ( protonated ) species . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Two cDNA clones encoding two different isoforms of the thyrotropin releasing hormone receptor ( TRH R ) from GH 3 rat anterior pituitary cells have been isolated . ^^^ One isoform corresponds to the TRH R ( 412 ) receptor previously described ( de la Pea , P . , Delgado , L . ^^^ The second one , named TRH R ( 387 ) , contains a 52 base pair deletion , which yields a new variant of the receptor protein 25 amino acid shorter and which contains 12 new residues on its carboxyl terminus . ^^^ Furthermore , the perfect colinearity between genomic DNA and TRH R ( 412 ) cDNA demonstrates that no other introns are present within the coding region of the TRH receptor gene . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We studied the effect of thyroid status on thyrotropin releasing hormone receptor ( TRH R ) mRNA levels both in vivo and in vitro ( GH 3 cells ) using a cloned rat TRH R cDNA by RT PCR . ^^^ TRH R mRNA levels in hypothyroid rats were also increased significantly compared with those of normal rats . ^^^ In GH 3 cells , however , no significant change of TRH R mRNA level was observed between cultures treated with triiodothyronine ( T 3 , 10 ( 9 ) and 10 ( 7 ) M ) and the untreated group . ^^^ The present data indicate that 1 ) the in vivo effects of thyroid status on TRH R mRNA levels differ from the in vitro one , and that 2 ) the down regulation of TRH R binding by thyroid hormone in GH 3 cells may be mediated by translational or post translational mechanisms . . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Xenopus oocytes that express mouse thyrotropin releasing hormone receptors ( TRH Rs ) after injection if RNA transcribed from TRH R cDNA respond to THR by a depolarizing current . ^^^ To determine whether there are functional differences between these proteins , we have co expressed the TRH R with either alpha 11 or alpha q . alpha 11 potentiated the response to TRH ( by 61 + / 16 % ) , while alpha q inhibited the response ( by 37 + / 9 % ) . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We showed previously that TRH down regulates TRH receptor ( TRH R ) mRNA in GH 3 cells by a mechanism that appears to be mediated by protein kinase C . ^^^ Here we show that vasoactive intestinal peptide ( VIP ) down regulates TRH R mRNA and present evidence that this action is mediated by protein kinase A . ^^^ In GH 3 cells , VIP caused a time and concentration dependent decrease in TRH R mRNA . ^^^ When cells were incubated with agents that elevate cAMP and TRH or phorbol 12 myristate 13 acetate , the decrease in TRH R mRNA was greater than with either agent alone . ^^^ We suggest that VIP , via protein kinase A , and TRH , via protein kinase C , dually regulate TRH R mRNA . . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| In a previous report we showed that TRH induced down regulation of the density of its receptors ( TRH Rs ) on rat pituitary tumor ( GH 3 ) cells was preceded by a decrease in the activity of the mRNA for the TRH R , as assayed in Xenopus oocytes . ^^^ Here we report the effects of TRH , elevation of cytoplasmic free Ca2+ concentration , phorbol myristate acetate ( PMA ) , and H 7 [ 1 ( 5 isoquinolinesulfonyl ) 2 methylpiperazine dihydrochloride ] , an inhibitor of protein kinases , on the levels of TRH R mRNA , which were measured by Northern analysis and in nuclease protection assays using probes made from mouse pituitary TRH R cDNA , in GH 3 cells . ^^^ TRH ( 1 microM TRH , a maximally effective dose ) caused a marked transient decrease in TRH R mRNA that attained a nadir of 20 45 % of control by 3 6 h , increased after 9 h , but was still below control levels after 24 h . ^^^ Elevation of the cytoplasmic free Ca2+ concentration had no effect on TRH R mRNA . ^^^ A maximally effective dose of PMA ( 1 microM ) caused decreases in TRH R mRNA that were similar in magnitude and time course to those induced by 1 microM TRH . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| In this study we measured the effects of TRH and elevation of cyclic AMP on TRH Rs expressed in non pituitary cells transfected with a recently cloned mouse pituitary TRH R complementary DNA . ^^^ In stably transfected rat glioma ( C 6 2 ) cells and transiently transfected COS 1 cells TRH caused TRH R down regulation while elevation of cyclic AMP caused increases in TRH R density . ^^^ Hence , the effects of cyclic AMP on TRH Rs in transfected C 6 2 and COS 1 cells are different from those in GH 3 cells while the effects of TRH on TRH R are similar in all three cell types . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We studied the mechanism by which thyrotropin releasing hormone ( TRH ) Gly stimulated prolactin and thyrotropin ( TSH ) secretion in pituitary , using a pituitary mammotropic cell line , GH 3 cells , and a cell line stably expressing a human TRH receptor ( TRH R ) . ^^^ In GH 3 cells expressing endogenous TRH R , an addition of TRH Gly evoked an immediate rise of intracellular calcium concentration , indicating that TRH Gly reacted directly without converting from TRH Gly to TRH . ^^^ In order to determine whether this reaction might occur through TRH R , we established a cell line stably expressing a human TRH R , by transfecting a human TRH R cDNA into Chinese hamster ovary cells ( CHO cells ) . ^^^ One micromolar and 100 nM TRH Gly also elevated intracellular concentration of calcium significantly , but not in CHO cells which were not transfected with the TRH R cDNA . ^^^ These data indicate that at high concentration , TRH Gly interacts directly with TRH R to activate signal transduction pathway , and that release of prolactin and TSH induced by TRH Gly in vitro may be due , at least in part , to the direct effect of TRH Gly on the TRH R . . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Binding sites for TRH are present in these tissues , but the TRH receptor ( TRH R ) has not been purified from any source . ^^^ Using Xenopus laevis oocytes in an expression cloning strategy , we have isolated a cDNA clone that encodes the mouse pituitary TRH R . ^^^ The 3 . 8 kilobase mouse TRH R cDNA encodes a protein of 393 amino acids that shows similarities to other guanine nucleotide binding regulatory protein coupled receptors . . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| The mechanism of TRH R downregulation was studied by monitoring TRH evoked depolarizing currents in Xenopus oocytes injected with GH 3 cell RNA as a bioassay for TRH R messenger RNA ( mRNA ) activity . ^^^ In GH 3 cells , TRH caused a rapid decrease in TRH R mRNA activity to 15 percent of control within 3 hours . ^^^ Because the half life of TRH R mRNA activity in control cells was approximately 3 hours , the rapid decrease in mRNA activity was not due to inhibition of mRNA synthesis alone and may represent a post transcriptional effect . . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Based on these results , we have formulated two receptor based hypotheses to explain AR : a ) rapid TRH R desensitization ( conversion to an inactive form ) by high but not low affinity TRH analogs ; and b ) a slower down regulation ( cellular internalization ) of the agonist receptor complex , most evident with high affinity agonists . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Since TRH has been linked to trophic events in the motor neuron and is being used for symptomatic treatment of motor neuron disorders , we have examined seven neural crest cell lines for TRH receptors ( TRH Rs ) and for the enzymes choline acetyltransferase ( ChAT ) and creatine kinase ( CK ) , with the intent to identify one that can be used for studies of TRH R mediated cellular events in the CNS . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| However , whether TRH receptors ( TRH R ) in the brain and retina are identical in structure with those in the anterior pituitary gland is presently unknown . ^^^ In this study , TRH R gene expression was examined by Northern blot analysis in the CNS and eye using a cloned rat pituitary TRH R cDNA . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We studied cellular calcium ( Ca ) mobilization and Ca entry from the medium following injection of various inositol phosphates ( IPs ) or activation of thyrotropin releasing hormone receptors ( TRH Rs ) in oocytes injected with TRH R cRNA . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Consecutive challenges with thyrotropin releasing hormone ( TRH ) of oocytes expressing the TRH receptor ( TRH R ) resulted in a pronounced desensitization , manifested as a decrease in chloride current amplitude and an increase in response latency . ^^^ A mutant of the TRH R that lacks protein kinase C consensus phosphorylation sites in the C terminal region , exhibited desensitization . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Comparison of the signalling properties of the long and short isoforms of the rat thyrotropin releasing hormone receptor following expression in rat 1 fibroblasts . cDNA species encoding either the long or the short isoforms of the rat thyrotropin releasing hormone ( TRH ) receptor were expressed stably in Rat 1 fibroblasts , and clones expressing specific binding of [ 3H ] TRH were detected and expanded . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Since the thyrotropin releasing hormone receptor ( TRH R ) cDNA was isolated , the distribution of TRH R mRNA has been investigated in the central nervous system ( CNS ) and the pituitary . ^^^ However , there has been less genetical studies on the distribution of TRH R mRNA in the peripheral tissues , although TRH exists not only in CNS but also in the peripheral tissues . ^^^ In this study we investigated the distribution of TRH R mRNA in rat peripheral tissues by reverse transcription polymerase chain reaction ( RT PCR ) and Northern blot analysis . ^^^ TRH R mRNA was detected in almost all of the peripheral tissues tested , although the amount varied considerably depending on the tissues . ^^^ In the uterus , thymus , ovary , and testis , TRH R mRNA levels appeared to be relatively high . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| The thyrotropin releasing hormone ( TRH ) receptor ( TRH R ) is a member of the seven transmembrane region , G protein coupled receptor family . ^^^ The affinity of the R306K TRH R was similar to that of the wild type ( WT ) TRH R , whereas no specific binding was detected in cells expressing R306A , R306E , or R306L TRH Rs . ^^^ The EC 50 values for stimulation of R306A , R306E , and R306L TRH Rs were 1500 , 1200 , and 3000 fold higher than that for the WT TRH R . ^^^ No specific binding was measurable in COS 1 cells expressing R283K , R283H , or R283A TRH Rs , whereas maximal TRH stimulation of IP formation was to levels 64 % , 42 % , or < 1 % , respectively , of that in cells expressing WT TRH Rs ; for R283K and R283H TRH Rs , EC 50 values were 6300 and 50 , 000 fold higher , respectively , than that for the WT TRH R . ^^^ In AtT 20 cells stably expressing R283A TRH Rs , the binding affinity was 39 , 000 fold lower than that of the WT TRH R and the number of receptors was estimated to be 0 . 88 10 10 ( 6 ) / cell , but TRH did not stimulate IP formation . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Regulation of the level of thyrotropin releasing hormone ( TRH ) receptor ( TRH R ) mRNA appears to involve both modulation of gene transcription and of mRNA degradation . ^^^ To study regulation of TRH R mRNA degradation and circumvent any physiological effect on transcription , we use cells stably transfected with mouse TRH R cDNA under control of the constitutively active cytomegalovirus promoter . ^^^ In stably transfected GH pituitary cells , we find that phorbol 12 myristate 13 acetate ( PMA ) , like TRH , down regulates TRH R mRNA by increasing the rate of TRH R mRNA degradation . ^^^ In contrast , in stably transfected AtT 20 pituitary cells and in nonpituitary cell lines , neither TRH nor PMA decreased TRH R mRNA levels . ^^^ These findings are consistent with the idea that activation of protein kinase C leads to enhanced degradation of TRH R mRNA in a cell type specific manner . . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| To investigate the potential roles of TRH in testicular function , characterization of TRH receptors ( TRH R ) in this tissue was undertaken . ^^^ Recently , a cDNA encoding murine TRH R has been isolated , making possible cloning of a rat TRH R cDNA from the anterior pituitary gland . ^^^ This cDNA was used for detection of TRH R gene expression in the rat testis by Northern blot analysis and reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ The concentration of TRH R mRNA in the testis was approximately 10 % of that in the pituitary . ^^^ TRH R mRNA was also detected by RT PCR in Metrizamide gradient purified Leydig cells . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We have examined the trafficking of the thyrotropin releasing hormone receptor ( TRHR ) and its ligand , after TRHR TRH internalization in rat pituitary GH4C1 cells . ^^^ TRHR entry into these pathways was not determined by the affinity of the receptor ligand interaction , because the extent of receptor recycling was similar after TRH and methyl TRH ( MeTRH ) induced internalization . ^^^ Unlike results with the TRHR , the TRH recycling pool was not depleted by the noncycling pathway . ^^^ The difference in the proportion of TRHR and MeTRH that were diverted into a noncycling pathway indicated intracellular dissociation of the internalized TRHR TRH complex . ^^^ Dissociation of the internalized TRHR TRH complex was dependent on the acidic pH in an intracellular compartment . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Production and characterization of polyclonal anti idiotypic anti TRH antibodies : application to the study of pituitary TRH receptor . cDNA encoding the thyrotropin releasing hormone receptor ( TRH R ) was recently cloned in rat pituitary prolactin cells and in mouse thyrotropes . ^^^ However , TRH R has not yet been purified to homogeneity and specific anti TRH R antibody could not yet be obtained by classical biochemical methods . ^^^ We thus attempted to obtain antibodies specific for TRH R using an anti idiotypic approach . ^^^ One of them , the polyclonal Ab 2 R38 / B12 , was tested for its ability to recognize the TRH R in rat pituitary , tumor derived , GH3 / B6 prolactin secreting cells . ^^^ These data suggest that we have characterized Ab 2 antibodies which recognize a molecular entity that might be related to the TRH R in GH3B6 cells . . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Endocytosis and recycling of both thyrotropin releasing hormone ( TRH ) and its G protein coupled receptor were visualized by conventional and confocal fluorescence microscopy in pituitary cells using a rhodamine labeled TRH analog ( Rhod TRH ) and indirect immunofluorescent staining of cells stably transfected with an epitope tagged TRH receptor ( TRHR ) . ^^^ Both Rhod TRH and TRHR were also localized on the plasma membrane after agonist binding at 0 degrees C . ^^^ Ligand binding at 37 degrees C resulted in rapid endocytosis , and both Rhod TRH and the epitope tagged TRHR appeared in cytoplasmic vesicles within 5 min . ^^^ Fluorescently labeled TRH and transferrin colocalized in the same endocytotic vesicles , and internalization of Rhod TRH and TRHR was inhibited by hypertonic medium , suggesting that endocytosis occurred by a clathrin dependent mechanism . ^^^ A mutant TRHR truncated at Cys 335 signaled but did not internalize Rhod TRH , confirming the importance of the carboxyl terminus of the TRHR in receptor mediated endocytosis . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We studied the activity of a truncated thyrotropin releasing hormone receptor ( TRH R ) , which lacks the last 59 amino acids of the carboxyl tail , where Cys 335 was mutated to a stop codon ( C335Stop ) ( Nussenzveig , D . ^^^ We conclude that a TRH R mutant truncated at Cys 335 exhibits constitutive activity that results in desensitization of the response to TRH . . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Activation of TRH receptors ( TRH R ) stimulates a signal transduction pathway that leads to the formation of two second messenger molecules , inositol 1 , 4 , 5 trisphosphate and 1 , 2 diacylglycerol . ^^^ As adenovirus mediated gene transfer allows expression of TRH R to high levels in a number of cell types , we tested again whether TRH R activation might elevate intracellular cAMP in these more sensitive cell systems . ^^^ In five cell lines , including three human lines , infection with a replication defective adenovirus that encodes the mouse TRH R complementary DNA ( AdCMVmTRHR ) induced the expression of 0 . 2 2 million TRH R / cell . ^^^ These data confirm that TRH R activation does not lead to an elevation of intracellular cAMP . . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| In cells infected with AdCMVmTRHR for 24 h , the size of the TRH responsive phosphoinositide pool increased with increasing TRH R expression . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Hybridization was carried out with a 32P labeled fragment of the human TRH R genomic DNA . ^^^ Hybridization of this probe to a human specific 10 . 5 kb DNA fragment of EcoRI digested WBC DNA was used to localize the human TRH R gene . ^^^ Results from 18 somatic cell hybrids corroborated unequivocally that the human TRH R gene can be assigned to human chromosome 8 . . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We have created a highly efficient adenovirus based expression vector for the thyrotropin releasing hormone ( TRH ) receptor ( TRH R ) , AdCMVmTRHR , to circumvent difficulties encountered when transient or stable plasmid expression systems are used . ^^^ Expression in several cell lines in culture reveals that rapid TRH R desensitization by TRH and phorbol 12 myristate 13 acetate is cell type specific . ^^^ The versatility of adenovirus mediated gene transfer and expression of TRH Rs not only facilitates in vitro studies of TRH R biology but also provides a valuable in vivo expression vector capable of extending TRH R studies to animal model systems . . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We have isolated a cDNA encoding the human pituitary TRH receptor ( TRH R ) protein with a predicted amino acid sequence of 398 amino acids . ^^^ Comparison of the amino acid sequences of the human TRH R with the previously published rodent TRH Rs showed that it is similar to both the rat and mouse TRH Rs , except that each species has variant amino acids at the carboxy ( COOH ) terminus . ^^^ The human TRH R belongs to the family of seven transmembrane domain , G protein coupled receptors , and it is believed that the COOH terminal region of this family of receptors may play an important role in receptor downregulation / internalisation , and possibly G protein coupling . ^^^ COS 1 cells expressing the human TRH R showed high affinity receptor binding . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Internalization of TRH receptor ( TRH R ) is dependent on sequences / structures in the receptor carboxyl terminal tail . ^^^ We constructed two mutant TRH Rs : delta 218 263 TRH R , in which most of the residues that form the putative third intracellular loop were deleted , and D71A TRH R , in which an Asp in the putative second transmembrane helix was mutated to Ala ; these TRH Rs did not activate PLC when expressed transiently in COS 1 cells . ^^^ We conclude that TRH R coupling to G protein and PLC increases the number of TRH Rs internalized at steady state even though the primary signals for agonist induced internalization are present in the receptor . ^^^ These data support the idea that a quaternary complex of TRH / TRH R / G protein / PLC is normally internalized . . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| In previous studies on the regulation of the endogenous TRH receptor ( TRHR ) in GH4C1 cells , we have shown that the synthetic glucocorticoid dexamethasone ( Dex ) increased TRHR abundance on the plasma membrane of these cells as well as increasing the concentration of TRHR mRNA . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Estradiol transcriptionally and posttranscriptionally up regulates thyrotropin releasing hormone receptor messenger ribonucleic acid in rat pituitary cells . 17 beta Estradiol ( E 2 ) has been shown to up regulate the binding activity of the TRH receptor in rat pituitary cells . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We tested the hypothesis that Tyr 106 of the third transmembrane helix of the TRH receptor ( TRH R ) binds pyroglutamyl of TRH by mutating Tyr 106 to Phe and replacing the ring carbonyl of the TRH pyroglutamyl moiety with a methylene group ( [ Pro 1 ] TRH ) . ^^^ Compared to the affinity of wild type TRH R for TRH , the affinities of [ Phe 106 ] TRH R for TRH and of wild type TRH R for [ Pro 1 ] TRH were 100 , 000 and 110 , 000 fold lower , respectively . ^^^ The affinity of [ Phe 106 ] TRH R for [ Pro 1 ] TRH was only 16 fold lower than that for TRH , demonstrating a lack of additivity of the effects of these changes in the receptor and ligand . ^^^ These data provide compelling evidence that the hydroxyl group of Tyr 106 of the TRH R binds the TRH pyroglutamyl carbonyl group . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| The cloning and characterization of the mouse TRH receptor ( TRH R ) gene revealed an untranslated exon ( exon 1 ) , a single intron and an upstream dinucleotide repeat sequence ( d ( TG ) 16 . d ( AG ) 21 ) in the 5 ' untranslated region ( UTR ) . ^^^ Exon 3 ( 228 bp ) corresponds exactly to a 228 bp deletion that exists in the rat TRH R cDNA , but not in the mouse cDNA . ^^^ The mouse TRH R cDNA encodes a protein of 393 amino acids which is 96 % homologous to the rat TRH R protein of 412 amino acids , but is 19 amino acids shorter at its COOH terminus . ^^^ The coding sequence for these 19 amino acids ( plus 1 extra amino acid ) does exist in the mouse TRH R gene , but the sequence is encoded by exon 4 , separated from the rest of the coding region by the stop codon and 223 bp of 3 ' UTR on exon 3 . ^^^ Splicing of exon 3 in the mouse TRH R gene would remove the last amino acid , the stop codon and the 223 bp of 3 ' UTR , allowing transcription to continue into the 3 ' UTR on exon 4 , which encodes the 19 extra amino acids found in the rat cDNA . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| The thyrotropin releasing hormone ( TRH ) TRH receptor ( TRHR ) complex undergoes rapid transformation in cells to an acid resistant form which appears to represent internalized agonist receptor complex . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We have isolated the TRH receptor ( TRH R ) from a rat anterior pituitary cDNA library , determined its sequence and examined its functional characteristics . ^^^ In TRH R transfected cells , TRH ( 100 nM ) produced an approximately twofold increase in total IP production . ^^^ In situ hybridization in the rat anterior pituitary revealed a heterogeneous distribution of label , a characteristic pattern of TRH R expression . ^^^ Over its length , the rat TRH R protein showed considerable homology with that of the mouse , except for a deletion of 232 bp in the 3 ' coding region . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Previous molecular studies on the mechanism of regulation of TRH receptor ( TRHR ) mRNA used transfected cells and concluded that the major mode of regulation is via mRNA degradation . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Using a homologous cDNA probe prepared from the TRHR cloned from these cells , we demonstrate here that TRH modulates the rate of transcription of TRHR mRNA . ^^^ Incubation of GH4C1 cells for 4 h with TRH caused an 80 % reduction in TRHR mRNA concentration . ^^^ The TRHR mRNA level remained low for 48 h in the continued presence of TRH . ^^^ Run on transcription assays demonstrated that TRH caused a decrease in TRHR mRNA transcription of about 60 % at 4 h . ^^^ Inhibition of protein synthesis did not prevent the TRH induced decrease in TRHR mRNA . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| A carboxyl terminus truncated mutant of the guanine nucleotide binding ( G ) protein coupled TRH receptor ( TRH R ) was previously shown to exhibit constitutive , i . e . ^^^ TRH independent , activity ( C335Stop TRH R ) . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| The ectopically expressed TRHR links to the phosphoinositide pathway , providing a means to regulate liver function with TRH , an extracellular ligand that does not normally affect hepatic function . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Thyrotropin releasing hormone ( TRH ) receptor ( TRH R ) complementary DNAs have been cloned from several species . ^^^ The deduced amino acid sequences are compatible with TRH R being a seven transmembrane spanning G protein coupled receptor . ^^^ These complementary DNAs and reagents derived from them have permitted detailed study of TRH R biology at the molecular and cellular levels . ^^^ Studies that have been performed since 1990 are reviewed in this article under the following headings : TRH R gene , tissue distribution of TRH R , primary structure of TRH Rs , three dimensional structure of the TRH R binding pocket , TRH R and G proteins , TRH R activation , TRH desensitization , TRH R endocytosis , and regulation of TRH R number . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We cloned a human thyrotropin releasing hormone receptor ( TRH R ) gene and its pituitary cDNA , and examined whether TRH R mRNA may be expressed and function in the GH secreting pituitary adenomas of patients with acromegaly . ^^^ The human TRH R consists of 398 amino acids and is a member of the G protein coupled receptor family . ^^^ Although highly homologous to the rat and mouse TRH Rs , the human TRH R has several differences in the carboxyl terminal structure . ^^^ The sequence and functioning analyses showed the same expression of TRH R mRNA in the pituitary adenomas as that in the normal pituitaries , indicating that 1 ) some adenomas of patients with acromegaly express an intact and functional TRH R , and that 2 ) the paradoxical response of GH secretion to TRH found in the patients might be a direct effect of TRH on TRH R expressed in the adenoma . . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| To assess the role of these TRH R Cys residues in disulfide bonding interactions , they were mutated to either Ser or Ala . ^^^ TRH R mutants Cys100Ser and Cys100Ala showed TRH binding affinities and IP activation similar to the wild type ( WT ) . ^^^ An epitope tag derived from the Haemophilus influenza hemagglutinin protein was incorporated at the NH 2 termini of the TRH R WT and TRH R Cys mutants to allow the independent assessment of cell surface expression of receptor protein . ^^^ TRH R mutants that failed to show receptor binding ( Cys98Ser , Cys98Ala , Cys179Ala ) showed WT levels of cell surface receptor expression , indicating that loss of receptor binding in these mutants is not attributable to loss of receptor expression . ^^^ Results obtained after chemical modification have shown that free sulfhydryl groups within the TRH R may also have a role in ligand interactions . . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We hypothesized that a subset of thyrotroph tumors might be caused by dominant somatic mutations that lead to inappropriate activation of the Gq / phospholipase C beta / Ca2+ / protein kinase C . pathway normally triggered by occupancy of the TRH receptor ( TRHR ) . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Thyrotropin releasing hormone receptor ( TRH R ) mRNA was detected in cryostat sections of the mouse testis using biotinylated oligonucleotides complementary to the cDNA encoding the mouse pituitary TRH R by in situ hybridization . ^^^ Thyrotropin releasing hormone receptor ( TRH R ) mRNA was detected in cryostat sections of the mouse testis using biotinylated oligonucleotides complementary to the cDNA encoding the mouse pituitary TRH R by in situ hybridization . ^^^ This result suggests that testicular TRH may serve as an autocrine regulator of reproductive function and development via TRH R in a fashion that is similar or identical to that in the pituitary . . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| To examine whether intact somatotrophs in the anterior pituitary also express TRH receptor , we attempted to localize both TRHR mRNA and GH immunoreactivity simultaneously . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| The native TRH receptor ( TRH R ) , which is a G protein coupled receptor that signals via the phosphoinositide transduction pathway , has been assumed to be inactive in the absence of agonist . ^^^ In contrast , a mutant mouse TRH R ( C335Stop TRH R ) was shown previously to exhibit constitutive ( or agonist independent ) signaling activity . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Glutamine 105 in the third transmembrane helix of the thyrotropin releasing hormone receptor ( TRH R ) occupies a position equivalent to a conserved negatively charged residue in receptors for biogenic amines where it acts as counterion interacting with the cationic amine moiety of the ligand . ^^^ Rapid dilution experiments following subsecond stimulation indicate that the TRH R is converted rapidly from a form showing fast dissociation kinetics to a form from which the hormone dissociates slowly . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Postnatal developmental change of the thyrotropin releasing hormone receptors ( TRHR ) in the rat forebrain was investigated using TRH binding assays and Northern blot analyses from postnatal day 8 to the age of 2 years . ^^^ These results indicated that : ( 1 ) TRH binding capacities in the forebrain increased to a maximum levels between the second and third postnatal week and thereafter decreased to adult level , ( 2 ) the levels of TRHR mRNA and the TRH binding capacities did not correlate in that period , suggesting that the TRHR number in the immature forebrain might be regulated by a posttranscriptional mechanism , and ( 3 ) expression of the TRHR gene in the forebrain and pituitary seemed to be regulated differentially during development . . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Most recently , TRH and TRH receptors ( TRH R ) , as well as their mRNAs , have been identified in rat testis . ^^^ To expand our knowledge on the testicular TRH and TRH receptor gene expression in different species , in the present study the mRNA levels of testicular TRH and TRH R were investigated in Siberian hamsters . ^^^ Messenger RNA levels of TRH and TRH R in the testes were determined by Northern blot analyses quantitated with densitometry scanning . ^^^ The results showed that specific TRH R mRNA , 3 . 8 kb in size , was identified in Siberian hamster testes and the mRNA levels were significantly elevated in the EDS treated testes compared to the controls ( p < 0 . 01 ) . ^^^ Our results demonstrate that both TRH and TRH R genes are expressed in Siberian hamster testes , and a significant increase of TRH R mRNA levels occurs in the Leydig cell eliminated hamster testes . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We measured the amounts of TRH receptor ( TRHR ) messenger ribonucleic acid ( mRNA ) in human normal pituitary and pituitary tumors and found a novel transcript of the TRHR gene . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| However , they differ significantly at their carboxy terminals , i . e . the mouse TRH R ends with an asparagine at position 393 while , in the rat , residue 393 is lysine and an additional 19 amino acids are added before the first stop codon . ^^^ As the mouse TRH R was cloned from thyrotrope derived TtT 97 tissue and the rat TRH R from lactotrope derived GH cell lines , we have investigated whether this difference at the carboxy terminus represents a species specific or cell type specific pattern of TRH R expression . ^^^ Reverse transcription PCR analysis was performed using primers that would generate DNA fragments including the stop codon in either the mouse or the rat TRH R and , in the mouse form , the extra 224 bp of 3 ' UT . ^^^ Sequence analysis revealed a 388 bp insertion at position 1663 in the 3 ' UT compared with the published mouse TRH R sequence . ^^^ Ribonuclease protection analysis using this 829 bp fragment as a probe showed that this sequence represented the major TRH R mRNA species in mouse pituitary and TtT 97 RNA . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| In this work , a model of the extracellular loops of the thyrotropin releasing hormone ( TRH ) receptor ( TRHR ) was constructed , and molecular dynamics simulations and quasi harmonic analysis have been performed to study the static and dynamic roles of the extracellular domain . ^^^ The static analysis based on curvature and electrostatic potential on the surface of TRHR suggests the formation of an initial recognition site between TRH and the surface of its receptor . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Thyrotropin releasing hormone ( TRH ) receptor ( TRHR ) cDNAs have been cloned from several species since 1990 . ^^^ Several new evidences have been reported including primary structure of TRHRs , distribution of TRHR mRNA , three dimensional structure of the TRH binding pocket , structure of the TRHR gene promoter , G proteins and TRHR etc . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We investigated the role of medullary TRH receptors in cold ( 4 6 C , 90 min ) induced stimulation of gastric motor function in fasted conscious rats using intracisternal injections of TRH receptor ( TRHr ) antisense oligodeoxynucleotides ( 100 microg twice , 48 and 24 h ) . ^^^ TRHr antisense , which had no effect on basal emptying , blocked TRH action but did not influence that of BIM 23052 . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| VSV TRHR GFP bound TRH with affinity similar to that of the unmodified receptor and stimulated [ 3H ] inositol phosphate production . ^^^ A clone stably expressing VSV TRHR GFP at some 120 , 000 copies / cell was selected to visualize this receptor during cellular exposure to TRH . ^^^ Hyperosmotic sucrose inhibited internalization of VSV TRHR GFP , measured both by intact cell [ 3H ] TRH binding studies and by confocal microscopy . ^^^ Now TRH caused a redistribution of VSV TRHR GFP to highly punctate but plasma membrane delineated foci . ^^^ After exposure to TRH substantial amounts of VSV TRHR GFP were present in vesicles overlapping those containing Texas Red transferrin . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| TRH R mRNA was identified also by reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We have studied the role of a highly conserved tryptophan and other aromatic residues of the thyrotropin releasing hormone ( TRH ) receptor ( TRH R ) that are predicted by computer modeling to form a hydrophobic cluster between transmembrane helix ( TM ) 5 and TM 6 . ^^^ The affinity of a mutant TRH R , in which Trp 279 was substituted by alanine ( W279A TRH R ) , for most tested agonists was higher than that of wild type ( WT ) TRH R , whereas its affinity for inverse agonists was diminished , suggesting that W279A TRH R is constitutively active . ^^^ We found that W279A TRH R exhibited 3 . 9 fold more signaling activity than WT TRH R in the absence of agonist . ^^^ Computer simulated models of the unoccupied WT TRH R , the TRH occupied WT TRH R , and various TRH R mutants predict that a hydrophobic cluster of residues , including Trp 279 ( TM 6 ) , Tyr 282 , and Phe 199 ( TM 5 ) , constrains the receptor in an inactive conformation . ^^^ We propose that a hydrophobic cluster including residues in TM 5 and TM 6 constrains the TRH R in an inactive conformation via interhelical interactions . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| The thyrotropin releasing hormone ( TRH ) receptor ( TRHR ) is widely distributed throughout the central and peripheral nervous systems . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| C335Stop is a constitutively active mutant of the TRH receptor ( TRH R ) . ^^^ To investigate the mechanism of the decreased responsiveness of C335Stop TRH R , we studied cellular Ca2+ concentrations ( [ Ca2+ ] 1 ) in AtT 20 cells stably transfected with C335Stop TRH R cDNA , or Ca2+ activated chloride currents in Xenopus laevis oocytes expressing this mutant receptor after injection of cRNA . ^^^ The competitive TRH R binding antagonist , chlorodiazepoxide ( CDE ) , was used as an inverse agonist to study the contribution of constitutive activity to desensitization . 2 . ^^^ CDE abolished heterologous desensitization induced by C335Stop TRH R on muscarinic m 1 receptor ( ml R ) co expressed in Xenopus oocytes . 4 . ^^^ We propose that cells expressing the constitutively active mutant TRH R rapidly desensitize their response , utilizing a mechanism mediated by an increase in [ Ca2+ ] 1 and PKC . . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Monoclonal anti rat thyrotropin releasing hormone ( TRH ) receptor ( TRHR ) specific antibodies ( mAb ) were generated by immunization with synthetic peptides of rat TRHR partial amino acid sequences ; one ( TRHR 01 ) was directed against a sequence ( 84 98 ) in the extracellular portion of the rat TRHR reported to be constant among different species , including man , and the second ( TRHR 02 ) recognizes the C terminal region sequence 399 412 . ^^^ Furthermore , TRHR 01 is agonistic in its ability to trigger Ca2+ flux , and desensitizes the TRH receptor . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Two types of rat TRH receptor ( TRH R 1 and TRH R 2 ) have been identified and shown previously to exhibit similar binding and stimulated signaling activity via the phosphoinositide calcium transduction pathway . ^^^ Since mouse TRH R 1 exhibits basal ( or constitutive or ligand independent ) signaling activity , we compared basal signaling by TRH R 1 and TRH R 2 . ^^^ We found that TRH R 2 exhibited higher basal signaling activity than TRH R 1 via pathways mediated by transcription factors AP 1 , Elk 1 and CREB . ^^^ Furthermore , CREB mediated transcription was directly dependent on the level of TRH R 2 expression and was inhibited by midazolam , a specific inverse agonist of basal TRH R signaling . ^^^ Since TRH R 1 and TRH R 2 exhibit distinct anatomic distributions in the rat , it is possible that TRH ligand independent signaling is more important in tissues / cells in which TRH R 2 is expressed and less important in tissues in which TRH R 1 is found . . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| In the present study , we characterized TRH receptors ( TRHR ) in mouse pancreatic islets and HIT T 15 cells , a hamster clonal beta cell line . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We studied rapid desensitization of the thyrotropin releasing hormone receptor ( TRH R ) or the m 1 muscarinic receptor ( m 1 R ) to a short challenge of threshold TRH concentration and persistent desensitization due to constitutive activity of a mutant TRH R . ^^^ In oocytes coexpressing wild type TRH Rs or m 1 Rs with a constitutively active TRH R mutant ( C335Stop TRH R ) , a persistent desensitization ( 33 57 % ) of the responses to TRH or ACh was observed . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We constructed deletion and site specific I 3 loop TRH R mutants and studied their binding and TRH stimulated signaling activities . ^^^ These data demonstrate that the juxtamembrane regions in the TRH R I 3 loop are important for coupling to Gq . . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Expression of thyrotropin releasing hormone receptor 2 ( TRH R 2 ) in the central nervous system of rats . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Within 5 min after TRH addition , the TRHR signal translocated from the plasma membrane to the cytoplasm of F4C1 cells transfected with TRHR cDNA . ^^^ Ten minutes after TRH addition , the TRHR signal formed aggregates in the cytoplasm . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Human TRH receptor ( TRHR ) belongs to the G protein coupled seven transmembrane domain receptor superfamily . ^^^ As it has been demonstrated that hypertensive patients have a blunted TSH response to TRH injection , suggesting a defect in the TRHR , we postulate that the TRHR gene is involved in human hypertension . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| OBJECTIVE : To investigate the expression regulation of thyrotrophin releasing hormone ( TRH ) and TRH receptor ( TRH R ) , and their role in the development of rat testis . ^^^ METHODS : Oligonucleotide primers were designed from the sequences of rat hypothalamus prepro TRH ( ppTRH ) and pituitary TRH R cDNA for reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ Specific fragments of ppTRH and TRH R cDNA were cloned and sequenced . ^^^ Expression plasmids containing ppTRH and TRH R genes were then constructed , and expression was found in E . coli DH 5 alpha . ppTRH and TRH R mRNA in the testis was quantitated in RNA samples prepared from rats at different developmental stages by real time quantitative RT PCR . ^^^ CONCLUSION : Our results suggest that rat testis could specifically express TRH and TRH R , and the transcriptions of ppTRH and TRH R genes in the rat testis were development dependent . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Thyrotropin releasing hormone receptor ( TRHR ) has already been cloned in mammals wherethyrotropin releasing hormone ( TRH ) is known to act as a powerful stimulator of thyroid stimulating hormone ( TSH ) secretion . ^^^ Thyrotropin releasing hormone receptor ( TRHR ) has already been cloned in mammals wherethyrotropin releasing hormone ( TRH ) is known to act as a powerful stimulator of thyroid stimulating hormone ( TSH ) secretion . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| If so , we wished to determine the impact of homo and hetero oligomerization on TRHR subtype trafficking as a potential mechanism for the differential cellular responses induced by TRH . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| A PCR approach was used to clone thyrotropin releasing hormone receptors ( TRH R ) from the brain and anterior pituitary of the teleost Catostomus commersoni ( cc ) , the white sucker . ^^^ Two distinct TRH R , designated ccTRH R 1 and ccTRH R 2 , were identified . ccTRH R 1 was similar to mammalian TRH R of the subtype 1 , whereas ccTRH R 2 exhibited the highest identity ( 61 % at the amino acid level ) with the recently discovered rat TRH R 2 . ^^^ It is postulated that ccTRH R 2 and rat TRH R 2 are members of the same TRH R subfamily 2 . ^^^ The analysis of genomic clones revealed , for the first time , both similarities and differences in the structure of TRH R subtype genes . ^^^ The position of this intron is highly conserved , as it was found at an identical position in the human TRH R 1 gene . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| In order to investigate the regulation of thyrotrophin releasing hormone receptor ( TRH R ) expression in rat testis , and to study their function in spermatogenesis , oligonucleotide primers were designed from the sequences of rat pituitary TRH R cDNA for reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ Specific fragments of TRH R cDNA were cloned . ^^^ DNA sequence analysis indicated that cDNA sequence of TRH R from rat testis was consistent with those of pituitary TRH R cDNA . ^^^ The non radioactive in situ hybridization ( NR ISH ) technique was applied to localize cells encoding TRH R mRNA in the rat testis . ^^^ TRH R mRNA in the testis was quantitated in RNA samples prepared from rats at different developmental stages by real time quantitative RT PCR . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Thyrotropin releasing hormone ( TRH ) receptor ( TRHR ) is a G protein coupled receptor playing a crucial role in the anterior pituitary where it controls the synthesis and secretion of thyroid stimulating hormone and prolactin . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Previously , three receptors , xTRHR 1 , xTRHR 2 , and xTRHR 3 , were cloned from brain tissue of Xenopus laevis with primers designed using sequences from the mammalian TRH receptor ( TRHR ) subtype 1 . ^^^ Our findings show differences between TRHR 1 and TRHR 2 from Xenopus and mammals and suggest that xTRHR 3 is a receptor for a ligand other than TRH . . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| In order to determine the mechanism by which these hypothalamic hormones modulate chicken TSH release , we examined the cellular localization of TRH receptors ( TRH R ) , CRH receptors type 1 ( CRH R 1 ) and somatostatin subtype 2 receptors ( SSTR 2 ) in the chicken pars distalis by in situ hybridization ( ISH ) , combined with immunological staining of thyrotropes . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| These studies were designed to characterize ubiquitination of the G protein coupled TRH receptor ( TRHR ) . ^^^ TRH induced a significant calcium response and rapid and extensive receptor internalization at both the permissive and nonpermissive temperatures , indicating that ligand dependent ubiquitination of the receptor , or any other protein , is not necessary for TRHR signaling or internalization . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Cells expressing both thyrotropin ( TSH ) and growth hormone ( GH ) are found in adult rat pituitary and in human pituitary adenomas in acromegaly , and these tumors contain both thyrotropin releasing hormone ( TRH ) and the TRH receptors ( TRHR ) . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| These data were then correlated with endocrinological and histological characteristics in 65 human pituitary adenomas including one non tumorous pituitary gland , to clarify the role of TRHR 1 and 2 gene expression in human pituitary adenomas , especially as it relates to the paradoxical stimulatory effects of TRH found in pituitary adenomas . ^^^ In examining the relationship between GH , PRL , TSH , or gonadotropin subunit response to TRH administration and TRHR gene expression , TRHR mRNA was found to be absent in 9 out of 10 GH cell adenomas without paradoxical GH response to TRH ( non responder ) , whereas TRHR genes were shown to be expressed in 10 out of 12 GH cell adenomas with paradoxical GH response to TRH ( responders ) ( chi 2 = 11 . 73 , p = 0 . 0009 ) . ^^^ However , there was no significant correlation between TRHR gene expression and responsiveness to PRL or gonadotropins to TRH administration in PRL cell adenomas ( chi 2 = 0 . 16 , p = 0 . 87 ) or gonadotroph cell adenomas ( chi 2 = 0 . 0006 , p = 1 ) , respectively . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| Here we assessed the localization in membrane domains of the epitope tagged , fluorescent version of thyrotropin releasing hormone receptor ( VSV TRH R GFP ) expressed in HEK 293 cells . ^^^ |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| We conclude that the efficacy differences of TRH analogs originated from the enhanced ability of TRH R complexed to the low affinity agonists to directly activate G protein ( s ) , and not by a modulation of the activity of accessory proteins , and propose possible mechanisms for this phenomenon . . ^^^ |
|
| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P20396 and P34981 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.63255846 |
| Here , we provide evidence for two additional direct interactions between TRH and TRH R . 0.63255846^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.54706077 |
| These data are consistent with the idea that there are initial interactions between TRH and the residues of a putative entry channel of TRH R . 0.54706077^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We studied the activity of a truncated thyrotropin releasing hormone receptor ( TRH R ) , which lacks the last 59 amino acids of the carboxyl tail , where Cys 335 was mutated to a stop codon ( C335Stop ) ( Nussenzveig , D . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We have examined the trafficking of the thyrotropin releasing hormone receptor ( TRHR ) and its ligand , after TRHR TRH internalization in rat pituitary GH4C1 cells . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Two cDNA clones encoding two different isoforms of the thyrotropin releasing hormone receptor ( TRH R ) from GH 3 rat anterior pituitary cells have been isolated . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We studied the effect of thyroid status on thyrotropin releasing hormone receptor ( TRH R ) mRNA levels both in vivo and in vitro ( GH 3 cells ) using a cloned rat TRH R cDNA by RT PCR . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Comparison of the signalling properties of the long and short isoforms of the rat thyrotropin releasing hormone receptor following expression in rat 1 fibroblasts . cDNA species encoding either the long or the short isoforms of the rat thyrotropin releasing hormone ( TRH ) receptor were expressed stably in Rat 1 fibroblasts , and clones expressing specific binding of [ 3H ] TRH were detected and expanded . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Since the thyrotropin releasing hormone receptor ( TRH R ) cDNA was isolated , the distribution of TRH R mRNA has been investigated in the central nervous system ( CNS ) and the pituitary . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Production and characterization of polyclonal anti idiotypic anti TRH antibodies : application to the study of pituitary TRH receptor . cDNA encoding the thyrotropin releasing hormone receptor ( TRH R ) was recently cloned in rat pituitary prolactin cells and in mouse thyrotropes . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Estradiol transcriptionally and posttranscriptionally up regulates thyrotropin releasing hormone receptor messenger ribonucleic acid in rat pituitary cells . 17 beta Estradiol ( E 2 ) has been shown to up regulate the binding activity of the TRH receptor in rat pituitary cells . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We cloned a human thyrotropin releasing hormone receptor ( TRH R ) gene and its pituitary cDNA , and examined whether TRH R mRNA may be expressed and function in the GH secreting pituitary adenomas of patients with acromegaly . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Thyrotropin releasing hormone receptor ( TRH R ) mRNA was detected in cryostat sections of the mouse testis using biotinylated oligonucleotides complementary to the cDNA encoding the mouse pituitary TRH R by in situ hybridization . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Glutamine 105 in the third transmembrane helix of the thyrotropin releasing hormone receptor ( TRH R ) occupies a position equivalent to a conserved negatively charged residue in receptors for biogenic amines where it acts as counterion interacting with the cationic amine moiety of the ligand . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We studied rapid desensitization of the thyrotropin releasing hormone receptor ( TRH R ) or the m 1 muscarinic receptor ( m 1 R ) to a short challenge of threshold TRH concentration and persistent desensitization due to constitutive activity of a mutant TRH R . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Expression of thyrotropin releasing hormone receptor 2 ( TRH R 2 ) in the central nervous system of rats . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Thyrotropin releasing hormone receptor ( TRHR ) has already been cloned in mammals wherethyrotropin releasing hormone ( TRH ) is known to act as a powerful stimulator of thyroid stimulating hormone ( TSH ) secretion . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Here we assessed the localization in membrane domains of the epitope tagged , fluorescent version of thyrotropin releasing hormone receptor ( VSV TRH R GFP ) expressed in HEK 293 cells . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We showed previously that the level of TRH receptor ( TRH R ) mRNA in rat pituitary GH 3 cells is down regulated by TRH . ^^^ Here , we study the mechanism of regulation of TRH R mRNA in a line of GH 3 cells that are stably transfected with mouse pituitary TRH R cDNA ( GH mTRHR 1 cells ) . ^^^ GH mTRHR 1 cells were found to have 2 . 4 times the number of TRH Rs and to stimulate a 2 . 5 fold greater increase in inositol phosphates in response to TRH than the parent cell line and to show TRH induced down regulation of TRH R number . ^^^ GH mTRHR 1 cells contained 26 + / 1 . 6 molecules of mouse TRH R mRNA / cell and 230 + / 31 molecules of mRNA for the neomycin resistance gene ( NEO ) with which it was cotransfected . ^^^ In GH mTRHR 1 cells , TRH caused a dose dependent transient decrease in mouse TRH R mRNA , with a nadir to 20 % of control levels after 6 h . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| In rat pituitary GH 3 cells , thyrotropin releasing hormone ( TRH ) down regulates TRH receptor ( TRH R ) mRNA ( Fujimoto , J . , Straub , R . ^^^ Here we show that TRH regulates RNase activity in GH 3 cells and that specific mRNA sequences are needed for in vivo regulation of TRH R mRNA by TRH . ^^^ This time course paralleled the effects of TRH on degradation of TRH R mRNA in vivo . ^^^ The regulated RNase activity was in a polysome free fraction of the lysates and was not specific for TRH R RNA . ^^^ A truncated form of TRH R RNA that was missing the entire 3 ' untranslated region ( TRHR R 5 ) was more stable than full length TRH R RNA ( TRHR WT ) . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We found previously that the level of endogenous TRH receptor ( TRH R ) mRNA in pituitary ( GH 3 ) cells and the level of mouse TRH R mRNA in GH 3 cells stably transfected with mouse pituitary TRH R cDNA are down regulated by TRH . ^^^ This down regulation is caused by TRH stimulation of TRH R mRNA degradation via a mechanism that appears to involve protein kinase C . ^^^ In this report we study regulation of TRH R mRNA in monkey kidney ( COS 1 ) cells transiently transfected with mouse pituitary TRH R cDNA . ^^^ In transfected COS 1 cells , TRH and phorbol 12 myristate 13 acetate ( PMA ) caused increases in the level of TRH R mRNA . ^^^ In contrast , TRH caused only a small transient increase in the level of the mRNA for the neomycin resistance gene , which was cotransfected with TRH R , and did not affect the level of the mRNA for glyceraldehyde phosphate dehydrogenase , an endogenous gene . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Thyrotropin releasing hormone , TRH ( < Glu His Proamide ) , and [ N tau Me His ] TRH ( MeTRH ) are present as neutral and positively charged forms at physiologic pH , and it was possible that they bind to the TRH receptor ( TRH R ) as charged ( protonated ) species . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Xenopus oocytes that express mouse thyrotropin releasing hormone receptors ( TRH Rs ) after injection if RNA transcribed from TRH R cDNA respond to THR by a depolarizing current . ^^^ To determine whether there are functional differences between these proteins , we have co expressed the TRH R with either alpha 11 or alpha q . alpha 11 potentiated the response to TRH ( by 61 + / 16 % ) , while alpha q inhibited the response ( by 37 + / 9 % ) . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We showed previously that TRH down regulates TRH receptor ( TRH R ) mRNA in GH 3 cells by a mechanism that appears to be mediated by protein kinase C . ^^^ Here we show that vasoactive intestinal peptide ( VIP ) down regulates TRH R mRNA and present evidence that this action is mediated by protein kinase A . ^^^ In GH 3 cells , VIP caused a time and concentration dependent decrease in TRH R mRNA . ^^^ When cells were incubated with agents that elevate cAMP and TRH or phorbol 12 myristate 13 acetate , the decrease in TRH R mRNA was greater than with either agent alone . ^^^ We suggest that VIP , via protein kinase A , and TRH , via protein kinase C , dually regulate TRH R mRNA . . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| The mechanism of TRH R downregulation was studied by monitoring TRH evoked depolarizing currents in Xenopus oocytes injected with GH 3 cell RNA as a bioassay for TRH R messenger RNA ( mRNA ) activity . ^^^ In GH 3 cells , TRH caused a rapid decrease in TRH R mRNA activity to 15 percent of control within 3 hours . ^^^ Because the half life of TRH R mRNA activity in control cells was approximately 3 hours , the rapid decrease in mRNA activity was not due to inhibition of mRNA synthesis alone and may represent a post transcriptional effect . . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| In a previous report we showed that TRH induced down regulation of the density of its receptors ( TRH Rs ) on rat pituitary tumor ( GH 3 ) cells was preceded by a decrease in the activity of the mRNA for the TRH R , as assayed in Xenopus oocytes . ^^^ Here we report the effects of TRH , elevation of cytoplasmic free Ca2+ concentration , phorbol myristate acetate ( PMA ) , and H 7 [ 1 ( 5 isoquinolinesulfonyl ) 2 methylpiperazine dihydrochloride ] , an inhibitor of protein kinases , on the levels of TRH R mRNA , which were measured by Northern analysis and in nuclease protection assays using probes made from mouse pituitary TRH R cDNA , in GH 3 cells . ^^^ TRH ( 1 microM TRH , a maximally effective dose ) caused a marked transient decrease in TRH R mRNA that attained a nadir of 20 45 % of control by 3 6 h , increased after 9 h , but was still below control levels after 24 h . ^^^ Elevation of the cytoplasmic free Ca2+ concentration had no effect on TRH R mRNA . ^^^ A maximally effective dose of PMA ( 1 microM ) caused decreases in TRH R mRNA that were similar in magnitude and time course to those induced by 1 microM TRH . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| In this study we measured the effects of TRH and elevation of cyclic AMP on TRH Rs expressed in non pituitary cells transfected with a recently cloned mouse pituitary TRH R complementary DNA . ^^^ In stably transfected rat glioma ( C 6 2 ) cells and transiently transfected COS 1 cells TRH caused TRH R down regulation while elevation of cyclic AMP caused increases in TRH R density . ^^^ Hence , the effects of cyclic AMP on TRH Rs in transfected C 6 2 and COS 1 cells are different from those in GH 3 cells while the effects of TRH on TRH R are similar in all three cell types . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Binding sites for TRH are present in these tissues , but the TRH receptor ( TRH R ) has not been purified from any source . ^^^ Using Xenopus laevis oocytes in an expression cloning strategy , we have isolated a cDNA clone that encodes the mouse pituitary TRH R . ^^^ The 3 . 8 kilobase mouse TRH R cDNA encodes a protein of 393 amino acids that shows similarities to other guanine nucleotide binding regulatory protein coupled receptors . . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Based on these results , we have formulated two receptor based hypotheses to explain AR : a ) rapid TRH R desensitization ( conversion to an inactive form ) by high but not low affinity TRH analogs ; and b ) a slower down regulation ( cellular internalization ) of the agonist receptor complex , most evident with high affinity agonists . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Since TRH has been linked to trophic events in the motor neuron and is being used for symptomatic treatment of motor neuron disorders , we have examined seven neural crest cell lines for TRH receptors ( TRH Rs ) and for the enzymes choline acetyltransferase ( ChAT ) and creatine kinase ( CK ) , with the intent to identify one that can be used for studies of TRH R mediated cellular events in the CNS . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We studied the mechanism by which thyrotropin releasing hormone ( TRH ) Gly stimulated prolactin and thyrotropin ( TSH ) secretion in pituitary , using a pituitary mammotropic cell line , GH 3 cells , and a cell line stably expressing a human TRH receptor ( TRH R ) . ^^^ In GH 3 cells expressing endogenous TRH R , an addition of TRH Gly evoked an immediate rise of intracellular calcium concentration , indicating that TRH Gly reacted directly without converting from TRH Gly to TRH . ^^^ In order to determine whether this reaction might occur through TRH R , we established a cell line stably expressing a human TRH R , by transfecting a human TRH R cDNA into Chinese hamster ovary cells ( CHO cells ) . ^^^ One micromolar and 100 nM TRH Gly also elevated intracellular concentration of calcium significantly , but not in CHO cells which were not transfected with the TRH R cDNA . ^^^ These data indicate that at high concentration , TRH Gly interacts directly with TRH R to activate signal transduction pathway , and that release of prolactin and TSH induced by TRH Gly in vitro may be due , at least in part , to the direct effect of TRH Gly on the TRH R . . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We studied cellular calcium ( Ca ) mobilization and Ca entry from the medium following injection of various inositol phosphates ( IPs ) or activation of thyrotropin releasing hormone receptors ( TRH Rs ) in oocytes injected with TRH R cRNA . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Consecutive challenges with thyrotropin releasing hormone ( TRH ) of oocytes expressing the TRH receptor ( TRH R ) resulted in a pronounced desensitization , manifested as a decrease in chloride current amplitude and an increase in response latency . ^^^ A mutant of the TRH R that lacks protein kinase C consensus phosphorylation sites in the C terminal region , exhibited desensitization . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| However , whether TRH receptors ( TRH R ) in the brain and retina are identical in structure with those in the anterior pituitary gland is presently unknown . ^^^ In this study , TRH R gene expression was examined by Northern blot analysis in the CNS and eye using a cloned rat pituitary TRH R cDNA . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| The thyrotropin releasing hormone ( TRH ) receptor ( TRH R ) is a member of the seven transmembrane region , G protein coupled receptor family . ^^^ The affinity of the R306K TRH R was similar to that of the wild type ( WT ) TRH R , whereas no specific binding was detected in cells expressing R306A , R306E , or R306L TRH Rs . ^^^ The EC 50 values for stimulation of R306A , R306E , and R306L TRH Rs were 1500 , 1200 , and 3000 fold higher than that for the WT TRH R . ^^^ No specific binding was measurable in COS 1 cells expressing R283K , R283H , or R283A TRH Rs , whereas maximal TRH stimulation of IP formation was to levels 64 % , 42 % , or < 1 % , respectively , of that in cells expressing WT TRH Rs ; for R283K and R283H TRH Rs , EC 50 values were 6300 and 50 , 000 fold higher , respectively , than that for the WT TRH R . ^^^ In AtT 20 cells stably expressing R283A TRH Rs , the binding affinity was 39 , 000 fold lower than that of the WT TRH R and the number of receptors was estimated to be 0 . 88 10 10 ( 6 ) / cell , but TRH did not stimulate IP formation . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Regulation of the level of thyrotropin releasing hormone ( TRH ) receptor ( TRH R ) mRNA appears to involve both modulation of gene transcription and of mRNA degradation . ^^^ To study regulation of TRH R mRNA degradation and circumvent any physiological effect on transcription , we use cells stably transfected with mouse TRH R cDNA under control of the constitutively active cytomegalovirus promoter . ^^^ In stably transfected GH pituitary cells , we find that phorbol 12 myristate 13 acetate ( PMA ) , like TRH , down regulates TRH R mRNA by increasing the rate of TRH R mRNA degradation . ^^^ In contrast , in stably transfected AtT 20 pituitary cells and in nonpituitary cell lines , neither TRH nor PMA decreased TRH R mRNA levels . ^^^ These findings are consistent with the idea that activation of protein kinase C leads to enhanced degradation of TRH R mRNA in a cell type specific manner . . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| To investigate the potential roles of TRH in testicular function , characterization of TRH receptors ( TRH R ) in this tissue was undertaken . ^^^ Recently , a cDNA encoding murine TRH R has been isolated , making possible cloning of a rat TRH R cDNA from the anterior pituitary gland . ^^^ This cDNA was used for detection of TRH R gene expression in the rat testis by Northern blot analysis and reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ The concentration of TRH R mRNA in the testis was approximately 10 % of that in the pituitary . ^^^ TRH R mRNA was also detected by RT PCR in Metrizamide gradient purified Leydig cells . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We have created a highly efficient adenovirus based expression vector for the thyrotropin releasing hormone ( TRH ) receptor ( TRH R ) , AdCMVmTRHR , to circumvent difficulties encountered when transient or stable plasmid expression systems are used . ^^^ Expression in several cell lines in culture reveals that rapid TRH R desensitization by TRH and phorbol 12 myristate 13 acetate is cell type specific . ^^^ The versatility of adenovirus mediated gene transfer and expression of TRH Rs not only facilitates in vitro studies of TRH R biology but also provides a valuable in vivo expression vector capable of extending TRH R studies to animal model systems . . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Endocytosis and recycling of both thyrotropin releasing hormone ( TRH ) and its G protein coupled receptor were visualized by conventional and confocal fluorescence microscopy in pituitary cells using a rhodamine labeled TRH analog ( Rhod TRH ) and indirect immunofluorescent staining of cells stably transfected with an epitope tagged TRH receptor ( TRHR ) . ^^^ Both Rhod TRH and TRHR were also localized on the plasma membrane after agonist binding at 0 degrees C . ^^^ Ligand binding at 37 degrees C resulted in rapid endocytosis , and both Rhod TRH and the epitope tagged TRHR appeared in cytoplasmic vesicles within 5 min . ^^^ Fluorescently labeled TRH and transferrin colocalized in the same endocytotic vesicles , and internalization of Rhod TRH and TRHR was inhibited by hypertonic medium , suggesting that endocytosis occurred by a clathrin dependent mechanism . ^^^ A mutant TRHR truncated at Cys 335 signaled but did not internalize Rhod TRH , confirming the importance of the carboxyl terminus of the TRHR in receptor mediated endocytosis . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Activation of TRH receptors ( TRH R ) stimulates a signal transduction pathway that leads to the formation of two second messenger molecules , inositol 1 , 4 , 5 trisphosphate and 1 , 2 diacylglycerol . ^^^ As adenovirus mediated gene transfer allows expression of TRH R to high levels in a number of cell types , we tested again whether TRH R activation might elevate intracellular cAMP in these more sensitive cell systems . ^^^ In five cell lines , including three human lines , infection with a replication defective adenovirus that encodes the mouse TRH R complementary DNA ( AdCMVmTRHR ) induced the expression of 0 . 2 2 million TRH R / cell . ^^^ These data confirm that TRH R activation does not lead to an elevation of intracellular cAMP . . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| In cells infected with AdCMVmTRHR for 24 h , the size of the TRH responsive phosphoinositide pool increased with increasing TRH R expression . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Hybridization was carried out with a 32P labeled fragment of the human TRH R genomic DNA . ^^^ Hybridization of this probe to a human specific 10 . 5 kb DNA fragment of EcoRI digested WBC DNA was used to localize the human TRH R gene . ^^^ Results from 18 somatic cell hybrids corroborated unequivocally that the human TRH R gene can be assigned to human chromosome 8 . . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We tested the hypothesis that Tyr 106 of the third transmembrane helix of the TRH receptor ( TRH R ) binds pyroglutamyl of TRH by mutating Tyr 106 to Phe and replacing the ring carbonyl of the TRH pyroglutamyl moiety with a methylene group ( [ Pro 1 ] TRH ) . ^^^ Compared to the affinity of wild type TRH R for TRH , the affinities of [ Phe 106 ] TRH R for TRH and of wild type TRH R for [ Pro 1 ] TRH were 100 , 000 and 110 , 000 fold lower , respectively . ^^^ The affinity of [ Phe 106 ] TRH R for [ Pro 1 ] TRH was only 16 fold lower than that for TRH , demonstrating a lack of additivity of the effects of these changes in the receptor and ligand . ^^^ These data provide compelling evidence that the hydroxyl group of Tyr 106 of the TRH R binds the TRH pyroglutamyl carbonyl group . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We have isolated a cDNA encoding the human pituitary TRH receptor ( TRH R ) protein with a predicted amino acid sequence of 398 amino acids . ^^^ Comparison of the amino acid sequences of the human TRH R with the previously published rodent TRH Rs showed that it is similar to both the rat and mouse TRH Rs , except that each species has variant amino acids at the carboxy ( COOH ) terminus . ^^^ The human TRH R belongs to the family of seven transmembrane domain , G protein coupled receptors , and it is believed that the COOH terminal region of this family of receptors may play an important role in receptor downregulation / internalisation , and possibly G protein coupling . ^^^ COS 1 cells expressing the human TRH R showed high affinity receptor binding . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Internalization of TRH receptor ( TRH R ) is dependent on sequences / structures in the receptor carboxyl terminal tail . ^^^ We constructed two mutant TRH Rs : delta 218 263 TRH R , in which most of the residues that form the putative third intracellular loop were deleted , and D71A TRH R , in which an Asp in the putative second transmembrane helix was mutated to Ala ; these TRH Rs did not activate PLC when expressed transiently in COS 1 cells . ^^^ We conclude that TRH R coupling to G protein and PLC increases the number of TRH Rs internalized at steady state even though the primary signals for agonist induced internalization are present in the receptor . ^^^ These data support the idea that a quaternary complex of TRH / TRH R / G protein / PLC is normally internalized . . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| In previous studies on the regulation of the endogenous TRH receptor ( TRHR ) in GH4C1 cells , we have shown that the synthetic glucocorticoid dexamethasone ( Dex ) increased TRHR abundance on the plasma membrane of these cells as well as increasing the concentration of TRHR mRNA . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Using a homologous cDNA probe prepared from the TRHR cloned from these cells , we demonstrate here that TRH modulates the rate of transcription of TRHR mRNA . ^^^ Incubation of GH4C1 cells for 4 h with TRH caused an 80 % reduction in TRHR mRNA concentration . ^^^ The TRHR mRNA level remained low for 48 h in the continued presence of TRH . ^^^ Run on transcription assays demonstrated that TRH caused a decrease in TRHR mRNA transcription of about 60 % at 4 h . ^^^ Inhibition of protein synthesis did not prevent the TRH induced decrease in TRHR mRNA . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| The cloning and characterization of the mouse TRH receptor ( TRH R ) gene revealed an untranslated exon ( exon 1 ) , a single intron and an upstream dinucleotide repeat sequence ( d ( TG ) 16 . d ( AG ) 21 ) in the 5 ' untranslated region ( UTR ) . ^^^ Exon 3 ( 228 bp ) corresponds exactly to a 228 bp deletion that exists in the rat TRH R cDNA , but not in the mouse cDNA . ^^^ The mouse TRH R cDNA encodes a protein of 393 amino acids which is 96 % homologous to the rat TRH R protein of 412 amino acids , but is 19 amino acids shorter at its COOH terminus . ^^^ The coding sequence for these 19 amino acids ( plus 1 extra amino acid ) does exist in the mouse TRH R gene , but the sequence is encoded by exon 4 , separated from the rest of the coding region by the stop codon and 223 bp of 3 ' UTR on exon 3 . ^^^ Splicing of exon 3 in the mouse TRH R gene would remove the last amino acid , the stop codon and the 223 bp of 3 ' UTR , allowing transcription to continue into the 3 ' UTR on exon 4 , which encodes the 19 extra amino acids found in the rat cDNA . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| The thyrotropin releasing hormone ( TRH ) TRH receptor ( TRHR ) complex undergoes rapid transformation in cells to an acid resistant form which appears to represent internalized agonist receptor complex . ^^^ |
|
| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We have isolated the TRH receptor ( TRH R ) from a rat anterior pituitary cDNA library , determined its sequence and examined its functional characteristics . ^^^ In TRH R transfected cells , TRH ( 100 nM ) produced an approximately twofold increase in total IP production . ^^^ In situ hybridization in the rat anterior pituitary revealed a heterogeneous distribution of label , a characteristic pattern of TRH R expression . ^^^ Over its length , the rat TRH R protein showed considerable homology with that of the mouse , except for a deletion of 232 bp in the 3 ' coding region . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Previous molecular studies on the mechanism of regulation of TRH receptor ( TRHR ) mRNA used transfected cells and concluded that the major mode of regulation is via mRNA degradation . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| A carboxyl terminus truncated mutant of the guanine nucleotide binding ( G ) protein coupled TRH receptor ( TRH R ) was previously shown to exhibit constitutive , i . e . ^^^ TRH independent , activity ( C335Stop TRH R ) . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| The ectopically expressed TRHR links to the phosphoinositide pathway , providing a means to regulate liver function with TRH , an extracellular ligand that does not normally affect hepatic function . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Thyrotropin releasing hormone ( TRH ) receptor ( TRH R ) complementary DNAs have been cloned from several species . ^^^ The deduced amino acid sequences are compatible with TRH R being a seven transmembrane spanning G protein coupled receptor . ^^^ These complementary DNAs and reagents derived from them have permitted detailed study of TRH R biology at the molecular and cellular levels . ^^^ Studies that have been performed since 1990 are reviewed in this article under the following headings : TRH R gene , tissue distribution of TRH R , primary structure of TRH Rs , three dimensional structure of the TRH R binding pocket , TRH R and G proteins , TRH R activation , TRH desensitization , TRH R endocytosis , and regulation of TRH R number . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| To assess the role of these TRH R Cys residues in disulfide bonding interactions , they were mutated to either Ser or Ala . ^^^ TRH R mutants Cys100Ser and Cys100Ala showed TRH binding affinities and IP activation similar to the wild type ( WT ) . ^^^ An epitope tag derived from the Haemophilus influenza hemagglutinin protein was incorporated at the NH 2 termini of the TRH R WT and TRH R Cys mutants to allow the independent assessment of cell surface expression of receptor protein . ^^^ TRH R mutants that failed to show receptor binding ( Cys98Ser , Cys98Ala , Cys179Ala ) showed WT levels of cell surface receptor expression , indicating that loss of receptor binding in these mutants is not attributable to loss of receptor expression . ^^^ Results obtained after chemical modification have shown that free sulfhydryl groups within the TRH R may also have a role in ligand interactions . . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We hypothesized that a subset of thyrotroph tumors might be caused by dominant somatic mutations that lead to inappropriate activation of the Gq / phospholipase C beta / Ca2+ / protein kinase C . pathway normally triggered by occupancy of the TRH receptor ( TRHR ) . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| To examine whether intact somatotrophs in the anterior pituitary also express TRH receptor , we attempted to localize both TRHR mRNA and GH immunoreactivity simultaneously . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| The native TRH receptor ( TRH R ) , which is a G protein coupled receptor that signals via the phosphoinositide transduction pathway , has been assumed to be inactive in the absence of agonist . ^^^ In contrast , a mutant mouse TRH R ( C335Stop TRH R ) was shown previously to exhibit constitutive ( or agonist independent ) signaling activity . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| However , they differ significantly at their carboxy terminals , i . e . the mouse TRH R ends with an asparagine at position 393 while , in the rat , residue 393 is lysine and an additional 19 amino acids are added before the first stop codon . ^^^ As the mouse TRH R was cloned from thyrotrope derived TtT 97 tissue and the rat TRH R from lactotrope derived GH cell lines , we have investigated whether this difference at the carboxy terminus represents a species specific or cell type specific pattern of TRH R expression . ^^^ Reverse transcription PCR analysis was performed using primers that would generate DNA fragments including the stop codon in either the mouse or the rat TRH R and , in the mouse form , the extra 224 bp of 3 ' UT . ^^^ Sequence analysis revealed a 388 bp insertion at position 1663 in the 3 ' UT compared with the published mouse TRH R sequence . ^^^ Ribonuclease protection analysis using this 829 bp fragment as a probe showed that this sequence represented the major TRH R mRNA species in mouse pituitary and TtT 97 RNA . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Postnatal developmental change of the thyrotropin releasing hormone receptors ( TRHR ) in the rat forebrain was investigated using TRH binding assays and Northern blot analyses from postnatal day 8 to the age of 2 years . ^^^ These results indicated that : ( 1 ) TRH binding capacities in the forebrain increased to a maximum levels between the second and third postnatal week and thereafter decreased to adult level , ( 2 ) the levels of TRHR mRNA and the TRH binding capacities did not correlate in that period , suggesting that the TRHR number in the immature forebrain might be regulated by a posttranscriptional mechanism , and ( 3 ) expression of the TRHR gene in the forebrain and pituitary seemed to be regulated differentially during development . . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Most recently , TRH and TRH receptors ( TRH R ) , as well as their mRNAs , have been identified in rat testis . ^^^ To expand our knowledge on the testicular TRH and TRH receptor gene expression in different species , in the present study the mRNA levels of testicular TRH and TRH R were investigated in Siberian hamsters . ^^^ Messenger RNA levels of TRH and TRH R in the testes were determined by Northern blot analyses quantitated with densitometry scanning . ^^^ The results showed that specific TRH R mRNA , 3 . 8 kb in size , was identified in Siberian hamster testes and the mRNA levels were significantly elevated in the EDS treated testes compared to the controls ( p < 0 . 01 ) . ^^^ Our results demonstrate that both TRH and TRH R genes are expressed in Siberian hamster testes , and a significant increase of TRH R mRNA levels occurs in the Leydig cell eliminated hamster testes . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We measured the amounts of TRH receptor ( TRHR ) messenger ribonucleic acid ( mRNA ) in human normal pituitary and pituitary tumors and found a novel transcript of the TRHR gene . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Thyrotropin releasing hormone ( TRH ) receptor ( TRHR ) cDNAs have been cloned from several species since 1990 . ^^^ Several new evidences have been reported including primary structure of TRHRs , distribution of TRHR mRNA , three dimensional structure of the TRH binding pocket , structure of the TRHR gene promoter , G proteins and TRHR etc . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We investigated the role of medullary TRH receptors in cold ( 4 6 C , 90 min ) induced stimulation of gastric motor function in fasted conscious rats using intracisternal injections of TRH receptor ( TRHr ) antisense oligodeoxynucleotides ( 100 microg twice , 48 and 24 h ) . ^^^ TRHr antisense , which had no effect on basal emptying , blocked TRH action but did not influence that of BIM 23052 . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| VSV TRHR GFP bound TRH with affinity similar to that of the unmodified receptor and stimulated [ 3H ] inositol phosphate production . ^^^ A clone stably expressing VSV TRHR GFP at some 120 , 000 copies / cell was selected to visualize this receptor during cellular exposure to TRH . ^^^ Hyperosmotic sucrose inhibited internalization of VSV TRHR GFP , measured both by intact cell [ 3H ] TRH binding studies and by confocal microscopy . ^^^ Now TRH caused a redistribution of VSV TRHR GFP to highly punctate but plasma membrane delineated foci . ^^^ After exposure to TRH substantial amounts of VSV TRHR GFP were present in vesicles overlapping those containing Texas Red transferrin . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| TRH R mRNA was identified also by reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| In this work , a model of the extracellular loops of the thyrotropin releasing hormone ( TRH ) receptor ( TRHR ) was constructed , and molecular dynamics simulations and quasi harmonic analysis have been performed to study the static and dynamic roles of the extracellular domain . ^^^ The static analysis based on curvature and electrostatic potential on the surface of TRHR suggests the formation of an initial recognition site between TRH and the surface of its receptor . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We have studied the role of a highly conserved tryptophan and other aromatic residues of the thyrotropin releasing hormone ( TRH ) receptor ( TRH R ) that are predicted by computer modeling to form a hydrophobic cluster between transmembrane helix ( TM ) 5 and TM 6 . ^^^ The affinity of a mutant TRH R , in which Trp 279 was substituted by alanine ( W279A TRH R ) , for most tested agonists was higher than that of wild type ( WT ) TRH R , whereas its affinity for inverse agonists was diminished , suggesting that W279A TRH R is constitutively active . ^^^ We found that W279A TRH R exhibited 3 . 9 fold more signaling activity than WT TRH R in the absence of agonist . ^^^ Computer simulated models of the unoccupied WT TRH R , the TRH occupied WT TRH R , and various TRH R mutants predict that a hydrophobic cluster of residues , including Trp 279 ( TM 6 ) , Tyr 282 , and Phe 199 ( TM 5 ) , constrains the receptor in an inactive conformation . ^^^ We propose that a hydrophobic cluster including residues in TM 5 and TM 6 constrains the TRH R in an inactive conformation via interhelical interactions . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| The thyrotropin releasing hormone ( TRH ) receptor ( TRHR ) is widely distributed throughout the central and peripheral nervous systems . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| C335Stop is a constitutively active mutant of the TRH receptor ( TRH R ) . ^^^ To investigate the mechanism of the decreased responsiveness of C335Stop TRH R , we studied cellular Ca2+ concentrations ( [ Ca2+ ] 1 ) in AtT 20 cells stably transfected with C335Stop TRH R cDNA , or Ca2+ activated chloride currents in Xenopus laevis oocytes expressing this mutant receptor after injection of cRNA . ^^^ The competitive TRH R binding antagonist , chlorodiazepoxide ( CDE ) , was used as an inverse agonist to study the contribution of constitutive activity to desensitization . 2 . ^^^ CDE abolished heterologous desensitization induced by C335Stop TRH R on muscarinic m 1 receptor ( ml R ) co expressed in Xenopus oocytes . 4 . ^^^ We propose that cells expressing the constitutively active mutant TRH R rapidly desensitize their response , utilizing a mechanism mediated by an increase in [ Ca2+ ] 1 and PKC . . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Monoclonal anti rat thyrotropin releasing hormone ( TRH ) receptor ( TRHR ) specific antibodies ( mAb ) were generated by immunization with synthetic peptides of rat TRHR partial amino acid sequences ; one ( TRHR 01 ) was directed against a sequence ( 84 98 ) in the extracellular portion of the rat TRHR reported to be constant among different species , including man , and the second ( TRHR 02 ) recognizes the C terminal region sequence 399 412 . ^^^ Furthermore , TRHR 01 is agonistic in its ability to trigger Ca2+ flux , and desensitizes the TRH receptor . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| In the present study , we characterized TRH receptors ( TRHR ) in mouse pancreatic islets and HIT T 15 cells , a hamster clonal beta cell line . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We constructed deletion and site specific I 3 loop TRH R mutants and studied their binding and TRH stimulated signaling activities . ^^^ These data demonstrate that the juxtamembrane regions in the TRH R I 3 loop are important for coupling to Gq . . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Within 5 min after TRH addition , the TRHR signal translocated from the plasma membrane to the cytoplasm of F4C1 cells transfected with TRHR cDNA . ^^^ Ten minutes after TRH addition , the TRHR signal formed aggregates in the cytoplasm . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Human TRH receptor ( TRHR ) belongs to the G protein coupled seven transmembrane domain receptor superfamily . ^^^ As it has been demonstrated that hypertensive patients have a blunted TSH response to TRH injection , suggesting a defect in the TRHR , we postulate that the TRHR gene is involved in human hypertension . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| A PCR approach was used to clone thyrotropin releasing hormone receptors ( TRH R ) from the brain and anterior pituitary of the teleost Catostomus commersoni ( cc ) , the white sucker . ^^^ Two distinct TRH R , designated ccTRH R 1 and ccTRH R 2 , were identified . ccTRH R 1 was similar to mammalian TRH R of the subtype 1 , whereas ccTRH R 2 exhibited the highest identity ( 61 % at the amino acid level ) with the recently discovered rat TRH R 2 . ^^^ It is postulated that ccTRH R 2 and rat TRH R 2 are members of the same TRH R subfamily 2 . ^^^ The analysis of genomic clones revealed , for the first time , both similarities and differences in the structure of TRH R subtype genes . ^^^ The position of this intron is highly conserved , as it was found at an identical position in the human TRH R 1 gene . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Two types of rat TRH receptor ( TRH R 1 and TRH R 2 ) have been identified and shown previously to exhibit similar binding and stimulated signaling activity via the phosphoinositide calcium transduction pathway . ^^^ Since mouse TRH R 1 exhibits basal ( or constitutive or ligand independent ) signaling activity , we compared basal signaling by TRH R 1 and TRH R 2 . ^^^ We found that TRH R 2 exhibited higher basal signaling activity than TRH R 1 via pathways mediated by transcription factors AP 1 , Elk 1 and CREB . ^^^ Furthermore , CREB mediated transcription was directly dependent on the level of TRH R 2 expression and was inhibited by midazolam , a specific inverse agonist of basal TRH R signaling . ^^^ Since TRH R 1 and TRH R 2 exhibit distinct anatomic distributions in the rat , it is possible that TRH ligand independent signaling is more important in tissues / cells in which TRH R 2 is expressed and less important in tissues in which TRH R 1 is found . . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| If so , we wished to determine the impact of homo and hetero oligomerization on TRHR subtype trafficking as a potential mechanism for the differential cellular responses induced by TRH . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| In order to investigate the regulation of thyrotrophin releasing hormone receptor ( TRH R ) expression in rat testis , and to study their function in spermatogenesis , oligonucleotide primers were designed from the sequences of rat pituitary TRH R cDNA for reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ Specific fragments of TRH R cDNA were cloned . ^^^ DNA sequence analysis indicated that cDNA sequence of TRH R from rat testis was consistent with those of pituitary TRH R cDNA . ^^^ The non radioactive in situ hybridization ( NR ISH ) technique was applied to localize cells encoding TRH R mRNA in the rat testis . ^^^ TRH R mRNA in the testis was quantitated in RNA samples prepared from rats at different developmental stages by real time quantitative RT PCR . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Thyrotropin releasing hormone ( TRH ) receptor ( TRHR ) is a G protein coupled receptor playing a crucial role in the anterior pituitary where it controls the synthesis and secretion of thyroid stimulating hormone and prolactin . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Previously , three receptors , xTRHR 1 , xTRHR 2 , and xTRHR 3 , were cloned from brain tissue of Xenopus laevis with primers designed using sequences from the mammalian TRH receptor ( TRHR ) subtype 1 . ^^^ Our findings show differences between TRHR 1 and TRHR 2 from Xenopus and mammals and suggest that xTRHR 3 is a receptor for a ligand other than TRH . . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| In order to determine the mechanism by which these hypothalamic hormones modulate chicken TSH release , we examined the cellular localization of TRH receptors ( TRH R ) , CRH receptors type 1 ( CRH R 1 ) and somatostatin subtype 2 receptors ( SSTR 2 ) in the chicken pars distalis by in situ hybridization ( ISH ) , combined with immunological staining of thyrotropes . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| OBJECTIVE : To investigate the expression regulation of thyrotrophin releasing hormone ( TRH ) and TRH receptor ( TRH R ) , and their role in the development of rat testis . ^^^ METHODS : Oligonucleotide primers were designed from the sequences of rat hypothalamus prepro TRH ( ppTRH ) and pituitary TRH R cDNA for reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ Specific fragments of ppTRH and TRH R cDNA were cloned and sequenced . ^^^ Expression plasmids containing ppTRH and TRH R genes were then constructed , and expression was found in E . coli DH 5 alpha . ppTRH and TRH R mRNA in the testis was quantitated in RNA samples prepared from rats at different developmental stages by real time quantitative RT PCR . ^^^ CONCLUSION : Our results suggest that rat testis could specifically express TRH and TRH R , and the transcriptions of ppTRH and TRH R genes in the rat testis were development dependent . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| Cells expressing both thyrotropin ( TSH ) and growth hormone ( GH ) are found in adult rat pituitary and in human pituitary adenomas in acromegaly , and these tumors contain both thyrotropin releasing hormone ( TRH ) and the TRH receptors ( TRHR ) . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| These data were then correlated with endocrinological and histological characteristics in 65 human pituitary adenomas including one non tumorous pituitary gland , to clarify the role of TRHR 1 and 2 gene expression in human pituitary adenomas , especially as it relates to the paradoxical stimulatory effects of TRH found in pituitary adenomas . ^^^ In examining the relationship between GH , PRL , TSH , or gonadotropin subunit response to TRH administration and TRHR gene expression , TRHR mRNA was found to be absent in 9 out of 10 GH cell adenomas without paradoxical GH response to TRH ( non responder ) , whereas TRHR genes were shown to be expressed in 10 out of 12 GH cell adenomas with paradoxical GH response to TRH ( responders ) ( chi 2 = 11 . 73 , p = 0 . 0009 ) . ^^^ However , there was no significant correlation between TRHR gene expression and responsiveness to PRL or gonadotropins to TRH administration in PRL cell adenomas ( chi 2 = 0 . 16 , p = 0 . 87 ) or gonadotroph cell adenomas ( chi 2 = 0 . 0006 , p = 1 ) , respectively . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| We conclude that the efficacy differences of TRH analogs originated from the enhanced ability of TRH R complexed to the low affinity agonists to directly activate G protein ( s ) , and not by a modulation of the activity of accessory proteins , and propose possible mechanisms for this phenomenon . . ^^^ |
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| Interacting proteins: P34981 and P20396 |
Pubmed |
SVM Score :0.0 |
| These studies were designed to characterize ubiquitination of the G protein coupled TRH receptor ( TRHR ) . ^^^ TRH induced a significant calcium response and rapid and extensive receptor internalization at both the permissive and nonpermissive temperatures , indicating that ligand dependent ubiquitination of the receptor , or any other protein , is not necessary for TRHR signaling or internalization . ^^^ |
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