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Gene Review

TRHR  -  thyrotropin-releasing hormone receptor

Homo sapiens

Synonyms: TRH-R, Thyroliberin receptor, Thyrotropin-releasing hormone receptor
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Disease relevance of TRHR


High impact information on TRHR


Chemical compound and disease context of TRHR


Biological context of TRHR

  • Cloning and sequence analysis of this short fragment revealed that the deleted sequence corresponded exactly to the 5'-sequence of exon 3, indicating alternative splicing of the TRHR mRNA [2].
  • As STRs detected in gene promoters are potential Z-DNA-forming sequences and seem to affect gene expression, we studied the potentially different transcriptional activity of these TRHR promoter variants and found that the S/-221C allele has a higher affinity than does the L/G-221 allele to nuclear protein factor(s) [5].
  • In search of molecular variants of TRHR, we disclosed that a polymorphic TG dinucleotide repeat (STR) at -68 bp and a novel single nucleotide polymorphism, a G-->C conversion at -221 located in the promoter of the TRHR are associated with essential hypertension [5].
  • By using this cDNA as a biotinylated probe, the gene encoding the TRH receptor has been localized to chromosome 8q23 by in situ hybridization [11].
  • The predicted amino acid sequence of the hTRH-R protein showed high homology with the rat and mouse TRH-Rs with the exception of their C-terminal region [12].

Anatomical context of TRHR


Associations of TRHR with chemical compounds


Physical interactions of TRHR

  • To further study TRH regulation of tau phosphorylation, immunoblotting was used to explore G-protein coupled TRH receptor activation of the phosphokinase C (PKC) and phosphokinase A (PKA) signaling pathways [21].
  • These results show that the TRH receptor itself does not need to bind beta-arrestin or undergo sequestration to activate MAPK but that the endocytic pathway must be intact [22].
  • Based on experimental data and the structural information acquired from computer simulations, we formulate a working hypothesis to describe the molecular events underlying the processes of TRH binding and TRH-R activation [23].
  • This proximal region apparently contains several promoter elements, including Pit-1 binding sequences within the first intron of the TRHR gene as previously reported [24].
  • Tamoxifen, an antiestrogenic compound, inhibited the increase in TRH receptor number induced by 0.3 nM 17 beta-estradiol and was capable of binding to the estrogen receptor [25].

Regulatory relationships of TRHR

  • TRHR immunofluorescence was expressed in many somatotrophs in normal rat pituitary and unlike immunoreactive GH, its expression was enhanced during hypothyroidism [4].
  • 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 [26].
  • Our observations indicate that Gq/11 is rapidly activated by the TRH receptor and that a second, unidentified, G protein is slowly activated by the TRH receptor [27].
  • 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) [28].

Other interactions of TRHR


Analytical, diagnostic and therapeutic context of TRHR


  1. Real time visualization of agonist-mediated redistribution and internalization of a green fluorescent protein-tagged form of the thyrotropin-releasing hormone receptor. Drmota, T., Gould, G.W., Milligan, G. J. Biol. Chem. (1998) [Pubmed]
  2. A novel transcript for the thyrotropin-releasing hormone receptor in human pituitary and pituitary tumors. Yamada, M., Hashimoto, K., Satoh, T., Shibusawa, N., Kohga, H., Ozawa, Y., Yamada, S., Mori, M. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  3. Gene expression study of thyrotropin releasing hormone (TRH) receptor using RT-PCR: relationship to clinical and immunohistochemical phenotypes in a series of human pituitary adenomas. Igarashi-Migitaka, J., Yamada, S., Hara, M., Sano, T., Ozawa, Y., Ohtani-Kaneko, R., Hirata, K. Endocr. J. (2003) [Pubmed]
  4. Somatotroph to thyrotroph cell transdifferentiation during experimental hypothyroidism - a light and electron-microscopy study. Radian, S., Coculescu, M., Morris, J.F. J. Cell. Mol. Med. (2003) [Pubmed]
  5. Thyrotropin-releasing hormone receptor (TRHR) gene is associated with essential hypertension. García, S.I., Porto, P.I., Dieuzeide, G., Landa, M.S., Kirszner, T., Plotquin, Y., Gonzalez, C., Pirola, C.J. Hypertension (2001) [Pubmed]
  6. Visualization of the thyrotropin-releasing hormone receptor and its ligand during endocytosis and recycling. Ashworth, R., Yu, R., Nelson, E.J., Dermer, S., Gershengorn, M.C., Hinkle, P.M. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  7. Casein kinase II sites in the intracellular C-terminal domain of the thyrotropin-releasing hormone receptor and chimeric gonadotropin-releasing hormone receptors contribute to beta-arrestin-dependent internalization. Hanyaloglu, A.C., Vrecl, M., Kroeger, K.M., Miles, L.E., Qian, H., Thomas, W.G., Eidne, K.A. J. Biol. Chem. (2001) [Pubmed]
  8. A disulfide bonding interaction role for cysteines in the extracellular domain of the thyrotropin-releasing hormone receptor. Cook, J.V., McGregor, A., Lee, T., Milligan, G., Eidne, K.A. Endocrinology (1996) [Pubmed]
  9. Prolonged agonist stimulation does not alter the protein composition of membrane domains in spite of dramatic changes induced in a specific signaling cascade. Matousek, P., Novotny, J., Rudajev, V., Svoboda, P. Cell Biochem. Biophys. (2005) [Pubmed]
  10. Resolution of G(s)alpha and G(q)alpha/G(11)alpha proteins in membrane domains by two-dimensional electrophoresis: the effect of long-term agonist stimulation. Matousek, P., Novotný, J., Svoboda, P. Physiological research / Academia Scientiarum Bohemoslovaca. (2004) [Pubmed]
  11. Assignment of the gene encoding the human thyrotropin-releasing hormone receptor to 8q23 by fluorescence in situ hybridization. Morrison, N., Duthie, S.M., Boyd, E., Eidne, K.A., Connor, J.M. Hum. Genet. (1994) [Pubmed]
  12. Molecular cloning of a functional human thyrotropin-releasing hormone receptor. Matre, V., Karlsen, H.E., Wright, M.S., Lundell, I., Fjeldheim, A.K., Gabrielsen, O.S., Larhammar, D., Gautvik, K.M. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  13. The human neuroendocrine thyrotropin-releasing hormone receptor promoter is activated by the haematopoietic transcription factor c-Myb. Matre, V., Høvring, P.I., Fjeldheim, A.K., Helgeland, L., Orvain, C., Andersson, K.B., Gautvik, K.M., Gabrielsen, O.S. Biochem. J. (2003) [Pubmed]
  14. The thyrotropin-releasing hormone-receptor complex and G11alpha are both internalised into clathrin-coated vesicles. Petrou, C., Tashjian, A.H. Cell. Signal. (1998) [Pubmed]
  15. Production and characterization of an antiserum which recognizes the native receptor for thyrotropin-releasing hormone. Chen, F., Selinger, Z., Marks, P., Belinsky, G., Tashjian, A.H. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  16. Assignment of human thyrotropin-releasing hormone (TRH) receptor gene to chromosome 8. Yamada, M., Monden, T., Konaka, S., Mori, M. Somat. Cell Mol. Genet. (1993) [Pubmed]
  17. Effect of cell type on the subcellular localization of the thyrotropin-releasing hormone receptor. Yu, R., Hinkle, P.M. Mol. Pharmacol. (1997) [Pubmed]
  18. Thyrotropin-releasing hormone receptor processing: role of ubiquitination and proteasomal degradation. Cook, L.B., Zhu, C.C., Hinkle, P.M. Mol. Endocrinol. (2003) [Pubmed]
  19. Thyrotropin-releasing hormone (TRH) receptor number determines the size of the TRH-responsive phosphoinositide pool. Demonstration using controlled expression of TRH receptors by adenovirus mediated gene transfer. Gershengorn, M.C., Heinflink, M., Nussenzveig, D.R., Hinkle, P.M., Falck-Pedersen, E. J. Biol. Chem. (1994) [Pubmed]
  20. A model of inverse agonist action at thyrotropin-releasing hormone receptor type 1: role of a conserved tryptophan in helix 6. Lu, X., Huang, W., Worthington, S., Drabik, P., Osman, R., Gershengorn, M.C. Mol. Pharmacol. (2004) [Pubmed]
  21. Thyrotropin releasing hormone inhibits tau phosphorylation by dual signaling pathways in hippocampal neurons. Luo, L., Stopa, E.G. J. Alzheimers Dis. (2004) [Pubmed]
  22. Activation of MAPK by TRH requires clathrin-dependent endocytosis and PKC but not receptor interaction with beta-arrestin or receptor endocytosis. Smith, J., Yu, R., Hinkle, P.M. Mol. Endocrinol. (2001) [Pubmed]
  23. Thyrotropin-releasing hormone and its receptors - A hypothesis for binding and receptor activation. Engel, S., Gershengorn, M.C. Pharmacol. Ther. (2007) [Pubmed]
  24. Transcription of the human thyrotropin-releasing hormone receptor gene-analysis of basal promoter elements and glucocorticoid response elements. Høvring, P.I., Matre, V., Fjeldheim, A.K., Loseth, O.P., Gautvik, K.M. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  25. Estrogens increase the number of thyrotropin-releasing hormone receptors on mammotropic cells in culture. Gershengorn, M.C., Marcus-Samuels, B.E., Geras, E. Endocrinology (1979) [Pubmed]
  26. Low Affinity Analogs of Thyrotropin-releasing Hormone Are Super-agonists. Engel, S., Neumann, S., Kaur, N., Monga, V., Jain, R., Northup, J., Gershengorn, M.C. J. Biol. Chem. (2006) [Pubmed]
  27. Kinetics and reversibility of thyrotropin-releasing hormone-stimulated guanine nucleotide exchange in membranes from GH4C1 cells. Brady, K.D., Han, B., Tashjian, A.H. Mol. Pharmacol. (1994) [Pubmed]
  28. Screening of candidate oncogenes in human thyrotroph tumors: absence of activating mutations of the G alpha q, G alpha 11, G alpha s, or thyrotropin-releasing hormone receptor genes. Dong, Q., Brucker-Davis, F., Weintraub, B.D., Smallridge, R.C., Carr, F.E., Battey, J., Spiegel, A.M., Shenker, A. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  29. Activation of the thyrotropin-releasing hormone (TRH) receptor by a direct precursor of TRH, TRH-Gly. Yamada, M., Iwasaki, T., Satoh, T., Monden, T., Konaka, S., Murakami, M., Iriuchijima, T., Mori, M. Neurosci. Lett. (1995) [Pubmed]
  30. Human TRH receptor messenger ribonucleic acid levels in normal and adenomatous pituitary: analysis by the competitive reverse transcription polymerase chain reaction method. Kaji, H., Xu, Y., Takahashi, Y., Abe, H., Tamaki, N., Chihara, K. Clin. Endocrinol. (Oxf) (1995) [Pubmed]
  31. The detection of thyrotropin-releasing hormone (TRH) and TRH receptor gene expression in Siberian hamster testes. Rao, J.N., Debeljuk, L., Bartke, A., Gao, Y.P., Wilber, J.F., Feng, P. Peptides (1997) [Pubmed]
  32. TRH receptor on immune cells: in vitro and in vivo stimulation of human lymphocyte and rat splenocyte DNA synthesis by TRH. Raiden, S., Polack, E., Nahmod, V., Labeur, M., Holsboer, F., Arzt, E. J. Clin. Immunol. (1995) [Pubmed]
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