IUPHAR/BPS Guide to Pharmacology CITE
https://doi.org/10.2218/gtopdb/F63/2019.4

Thyrotropin-releasing hormone receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database



Anthony P. Davenport1, Marvin Gershengorn2 and Rebecca Hills3
  1. University of Cambridge, UK
  2. National Institutes of Health, USA
  3. University of Edinburgh, UK


Abstract

Thyrotropin-releasing hormone (TRH) receptors (provisional nomenclature as recommended by NC-IUPHAR [13]) are activated by the endogenous tripeptide TRH (pGlu-His-ProNH2). TRH and TRH analogues fail to distinguish TRH1 and TRH2 receptors [28]. [3H]TRH (human, mouse, rat) is able to label both TRH1 and TRH2 receptors with Kd values of 13 and 9 nM respectively. Synthesis and biology of ring-modified L-Histidine containing TRH analogues has been reported [22].

Contents

This is a citation summary for Thyrotropin-releasing hormone receptors in the Guide to Pharmacology database (GtoPdb). It exists purely as an adjunct to the database to facilitate the recognition of citations to and from the database by citation analyzers. Readers will almost certainly want to visit the relevant sections of the database which are given here under database links.

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Database links

Thyrotropin-releasing hormone receptors
http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=63
Introduction to Thyrotropin-releasing hormone receptors
http://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=63
    Receptors
            TRH1 receptor
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=363
            TRH2 receptor
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=754

References

  1. Aragay AM, Katz A and Simon MI. (1992) The G alpha q and G alpha 11 proteins couple the thyrotropin-releasing hormone receptor to phospholipase C in GH3 rat pituitary cells. J. Biol. Chem. 267: 24983-8 [PMID:1334076]
  2. Boler J, Enzmann F, Folkers K, Bowers CY and Schally AV. (1969) The identity of chemical and hormonal properties of the thyrotropin releasing hormone and pyroglutamyl-histidyl-proline amide. Biochem. Biophys. Res. Commun. 37: 705-10 [PMID:4982117]
  3. Bonomi M, Busnelli M, Beck-Peccoz P, Costanzo D, Antonica F, Dolci C, Pilotta A, Buzi F and Persani L. (2009) A family with complete resistance to thyrotropin-releasing hormone. N. Engl. J. Med. 360: 731-4 [PMID:19213692]
  4. Burgus R, Dunn TF, Desiderio D, Ward DN, Vale W and Guillemin R. (1970) Characterization of ovine hypothalamic hypophysiotropic TSH-releasing factor. Nature 226: 321-5 [PMID:4985794]
  5. Calzá L, Giardino L, Ceccatelli S, Zanni M, Elde R and Hökfelt T. (1992) Distribution of thyrotropin-releasing hormone receptor messenger RNA in the rat brain: an in situ hybridization study. Neuroscience 51: 891-909 [PMID:1488129]
  6. Cao J, O'Donnell D, Vu H, Payza K, Pou C, Godbout C, Jakob A, Pelletier M, Lembo P and Ahmad S et al.. (1998) Cloning and characterization of a cDNA encoding a novel subtype of rat thyrotropin-releasing hormone receptor. J. Biol. Chem. 273: 32281-7 [PMID:9822707]
  7. Collu R, Tang J, Castagné J, Lagacé G, Masson N, Huot C, Deal C, Delvin E, Faccenda E and Eidne KA et al.. (1997) A novel mechanism for isolated central hypothyroidism: inactivating mutations in the thyrotropin-releasing hormone receptor gene. J. Clin. Endocrinol. Metab. 82: 1561-5 [PMID:9141550]
  8. de la Peña P, Delgado LM, del Camino D and Barros F. (1992) Cloning and expression of the thyrotropin-releasing hormone receptor from GH3 rat anterior pituitary cells. Biochem. J. 284 ( Pt 3): 891-9 [PMID:1377915]
  9. Drummond AH, Hughes PJ, Ruiz-Larrea F and Joels LA. (1989) Use of receptor antagonist in elucidating the mechanism of action of TRH in GH3 cells. Ann. N. Y. Acad. Sci. 553: 197-204 [PMID:2566295]
  10. Duthie SM, Taylor PL, Anderson L, Cook J and Eidne KA. (1993) Cloning and functional characterisation of the human TRH receptor. Mol. Cell. Endocrinol. 95: R11-5 [PMID:8243797]
  11. Engel S, Neumann S, Kaur N, Monga V, Jain R, Northup J and Gershengorn MC. (2006) Low affinity analogs of thyrotropin-releasing hormone are super-agonists. J. Biol. Chem. 281: 13103-9 [PMID:16551618]
  12. Engel S, Skoumbourdis AP, Childress J, Neumann S, Deschamps JR, Thomas CJ, Colson AO, Costanzi S and Gershengorn MC. (2008) A virtual screen for diverse ligands: discovery of selective G protein-coupled receptor antagonists. J. Am. Chem. Soc. 130: 5115-23 [PMID:18357984]
  13. Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP, Spedding M and Harmar AJ. (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol. Rev. 57: 279-88 [PMID:15914470]
  14. Geras-Raaka E and Gershengorn MC. (1987) Measurement of changes in cellular calcium metabolism in response to thyrotropin-releasing hormone. Meth. Enzymol. 141: 36-53 [PMID:3110553]
  15. Gershengorn MC and Osman R. (1996) Molecular and cellular biology of thyrotropin-releasing hormone receptors. Physiol. Rev. 76: 175-91 [PMID:8592728]
  16. Harder S, Lu X, Wang W, Buck F, Gershengorn MC and Bruhn TO. (2001) Regulator of G protein signaling 4 suppresses basal and thyrotropin releasing-hormone (TRH)-stimulated signaling by two mouse TRH receptors, TRH-R(1) and TRH-R(2). Endocrinology 142: 1188-94 [PMID:11181534]
  17. Hollenberg AN. (2008) The role of the thyrotropin-releasing hormone (TRH) neuron as a metabolic sensor. Thyroid 18: 131-9 [PMID:18279013]
  18. Hsieh KP and Martin TF. (1992) Thyrotropin-releasing hormone and gonadotropin-releasing hormone receptors activate phospholipase C by coupling to the guanosine triphosphate-binding proteins Gq and G11. Mol. Endocrinol. 6: 1673-81 [PMID:1333052]
  19. Imai A and Gershengorn MC. (1987) Measurement of lipid turnover in response to thyrotropin-releasing hormone. Meth. Enzymol. 141: 100-1 [PMID:3037241]
  20. Itadani H, Nakamura T, Itoh J, Iwaasa H, Kanatani A, Borkowski J, Ihara M and Ohta M. (1998) Cloning and characterization of a new subtype of thyrotropin-releasing hormone receptors. Biochem. Biophys. Res. Commun. 250: 68-71 [PMID:9735333]
  21. Matre V, Karlsen HE, Wright MS, Lundell I, Fjeldheim AK, Gabrielsen OS, Larhammar D and Gautvik KM. (1993) Molecular cloning of a functional human thyrotropin-releasing hormone receptor. Biochem. Biophys. Res. Commun. 195: 179-85 [PMID:8395824]
  22. Meena CL, Thakur A, Nandekar PP, Sharma SS, Sangamwar AT and Jain R. (2016) Synthesis and biology of ring-modified l-Histidine containing thyrotropin-releasing hormone (TRH) analogues. Eur J Med Chem 111: 72-83 [PMID:26854379]
  23. O'Dowd BF, Lee DK, Huang W, Nguyen T, Cheng R, Liu Y, Wang B, Gershengorn MC and George SR. (2000) TRH-R2 exhibits similar binding and acute signaling but distinct regulation and anatomic distribution compared with TRH-R1. Mol. Endocrinol. 14: 183-93 [PMID:10628757]
  24. Perret G, Valensi P, Hugues JN, Vassy R and Uzzan B. (1988) Use of a pharmacokinetic model to characterize the thyrotropin (TSH) and prolactin (PRL) response to thyrotropin-releasing hormone (THR) in man. Methods Find Exp Clin Pharmacol 10: 387-91 [PMID:3137402]
  25. Rabeler R, Mittag J, Geffers L, Rüther U, Leitges M, Parlow AF, Visser TJ and Bauer K. (2004) Generation of thyrotropin-releasing hormone receptor 1-deficient mice as an animal model of central hypothyroidism. Mol. Endocrinol. 18: 1450-60 [PMID:14988432]
  26. Regard JB, Sato IT and Coughlin SR. (2008) Anatomical profiling of G protein-coupled receptor expression. Cell 135: 561-71 [PMID:18984166]
  27. Straub RE, Frech GC, Joho RH and Gershengorn MC. (1990) Expression cloning of a cDNA encoding the mouse pituitary thyrotropin-releasing hormone receptor. Proc. Natl. Acad. Sci. U.S.A. 87: 9514-8 [PMID:2175902]
  28. Sun Y, Lu X and Gershengorn MC. (2003) Thyrotropin-releasing hormone receptors -- similarities and differences. J. Mol. Endocrinol. 30: 87-97 [PMID:12683933]
  29. Sun Y, Zupan B, Raaka BM, Toth M and Gershengorn MC. (2009) TRH-receptor-type-2-deficient mice are euthyroid and exhibit increased depression and reduced anxiety phenotypes. Neuropsychopharmacology 34: 1601-8 [PMID:19078951]
  30. Taylor RL and Burt DR. (1981) Preparation of 3H-[3-M3-His2]TRH as an improved ligand for TRH receptors. Neuroendocrinology 32: 310-6 [PMID:6264336]
  31. Thirunarayanan N, Nir EA, Raaka BM and Gershengorn MC. (2013) Thyrotropin-releasing hormone receptor type 1 (TRH-R1), not TRH-R2, primarily mediates taltirelin actions in the CNS of mice. Neuropsychopharmacology 38: 950-6 [PMID:23303050]
  32. Thirunarayanan N, Raaka BM and Gershengorn MC. (2012) Taltirelin is a superagonist at the human thyrotropin-releasing hormone receptor. Front Endocrinol (Lausanne) 3: 120 [PMID:23087672]
  33. Vale W, Rivier J and Burgus R. (1971) Synthetic TRF (thyrotropin releasing factor) analogues. II. pGlu-N3imMe-His-Pro-NH2: a synthetic analogue with specific activity greater than that of TRF2. Endocrinology 89: 1485-8 [PMID:5001013]
  34. Wang W and Gershengorn MC. (1999) Rat TRH receptor type 2 exhibits higher basal signaling activity than TRH receptor type 1. Endocrinology 140: 4916-9 [PMID:10499553]
  35. Zabavnik J, Arbuthnott G and Eidne KA. (1993) Distribution of thyrotrophin-releasing hormone receptor messenger RNA in rat pituitary and brain. Neuroscience 53: 877-87 [PMID:8387653]
  36. Zeng H, Schimpf BA, Rohde AD, Pavlova MN, Gragerov A and Bergmann JE. (2007) Thyrotropin-releasing hormone receptor 1-deficient mice display increased depression and anxiety-like behavior. Mol. Endocrinol. 21: 2795-804 [PMID:17666589]
  37. Zhao D, Yang J, Jones KE, Gerald C, Suzuki Y, Hogan PG, Chin WW and Tashjian Jr AH. (1992) Molecular cloning of a complementary deoxyribonucleic acid encoding the thyrotropin-releasing hormone receptor and regulation of its messenger ribonucleic acid in rat GH cells. Endocrinology 130: 3529-36 [PMID:1317787]