Thyrotropin-releasing hormone receptor explained

Thyrotropin-releasing hormone receptor (TRHR) is a G protein-coupled receptor which binds thyrotropin-releasing hormone.^{[1] [2]}

The TRHR is found on the cell membrane of thyrotropes of the anterior pituitary. When the TRHR is activated it associates with a G_αq/11 protein. The TRHR-G protein complex then activates phospholipase C, which causes the formation of inositol triphosphate (IP3) and diacylglycerol (DAG). This leads to an increase in cytoplasmic calcium ion concentrations which stimulates the exocytosis of thyroid-stimulating hormone (TSH) into the blood.

Further reading

• Yamada M, Iwasaki T, Satoh T, Monden T, Konaka S, Murakami M, Iriuchijima T, Mori M . Activation of the thyrotropin-releasing hormone (TRH) receptor by a direct precursor of TRH, TRH-Gly . Neuroscience Letters . 196 . 1–2 . 109–12 . August 1995 . 7501234 . 10.1016/0304-3940(95)11861-P . 45874879 .
• Hinuma S, Hosoya M, Ogi K, Tanaka H, Nagai Y, Onda H . Molecular cloning and functional expression of a human thyrotropin-releasing hormone (TRH) receptor gene . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1219 . 2 . 251–9 . October 1994 . 7918619 . 10.1016/0167-4781(94)90046-9 .
• Morrison N, Duthie SM, Boyd E, Eidne KA, Connor JM . Assignment of the gene encoding the human thyrotropin-releasing hormone receptor to 8q23 by fluorescence in situ hybridization . Human Genetics . 93 . 6 . 716–8 . June 1994 . 8005602 . 10.1007/bf00201580 . 804377 .
• Yamada M, Monden T, Konaka S, Mori M . Assignment of human thyrotropin-releasing hormone (TRH) receptor gene to chromosome 8 . Somatic Cell and Molecular Genetics . 19 . 6 . 577–80 . November 1993 . 8128317 . 10.1007/BF01233384 . 44982871 .
• Duthie SM, Taylor PL, Anderson L, Cook J, Eidne KA . Cloning and functional characterisation of the human TRH receptor . Molecular and Cellular Endocrinology . 95 . 1–2 . R11-5 . September 1993 . 8243797 . 10.1016/0303-7207(93)90043-J . 21150474 .
• Matre V, Karlsen HE, Wright MS, Lundell I, Fjeldheim AK, Gabrielsen OS, Larhammar D, Gautvik KM . Molecular cloning of a functional human thyrotropin-releasing hormone receptor . Biochemical and Biophysical Research Communications . 195 . 1 . 179–85 . August 1993 . 8395824 . 10.1006/bbrc.1993.2027 .
• Yamada M, Monden T, Satoh T, Satoh N, Murakami M, Iriuchijima T, Kakegawa T, Mori M . Pituitary adenomas of patients with acromegaly express thyrotropin-releasing hormone receptor messenger RNA: cloning and functional expression of the human thyrotropin-releasing hormone receptor gene . Biochemical and Biophysical Research Communications . 195 . 2 . 737–45 . September 1993 . 8396925 . 10.1006/bbrc.1993.2107 .
• Iwasaki T, Yamada M, Satoh T, Konaka S, Ren Y, Hashimoto K, Kohga H, Kato Y, Mori M . Genomic organization and promoter function of the human thyrotropin-releasing hormone receptor gene . The Journal of Biological Chemistry . 271 . 36 . 22183–8 . September 1996 . 8703031 . 10.1074/jbc.271.36.22183 . free .
• Cook JV, McGregor A, Lee T, Milligan G, Eidne KA . A disulfide bonding interaction role for cysteines in the extracellular domain of the thyrotropin-releasing hormone receptor . Endocrinology . 137 . 7 . 2851–8 . July 1996 . 8770906 . 10.1210/endo.137.7.8770906 . free .
• Collu R, Tang J, Castagné J, Lagacé G, Masson N, Huot C, Deal C, Delvin E, Faccenda E, Eidne KA, Van Vliet G . A novel mechanism for isolated central hypothyroidism: inactivating mutations in the thyrotropin-releasing hormone receptor gene . The Journal of Clinical Endocrinology and Metabolism . 82 . 5 . 1561–5 . May 1997 . 10.1210/jcem.82.5.3918 . 9141550 . 18861350 . free .
• Petrou C, Tashjian AH . The thyrotropin-releasing hormone-receptor complex and G11alpha are both internalised into clathrin-coated vesicles . Cellular Signalling . 10 . 8 . 553–9 . September 1998 . 9794253 . 10.1016/S0898-6568(97)00190-3 .
• Matre V, Høvring PI, Orstavik S, Frengen E, Rian E, Velickovic Z, Murray-McIntosh RP, Gautvik KM . Structural and functional organization of the gene encoding the human thyrotropin-releasing hormone receptor . Journal of Neurochemistry . 72 . 1 . 40–50 . January 1999 . 9886052 . 10.1046/j.1471-4159.1999.0720040.x . 6665620 . free .
• Kroeger KM, Hanyaloglu AC, Seeber RM, Miles LE, Eidne KA . Constitutive and agonist-dependent homo-oligomerization of the thyrotropin-releasing hormone receptor. Detection in living cells using bioluminescence resonance energy transfer . The Journal of Biological Chemistry . 276 . 16 . 12736–43 . April 2001 . 11278883 . 10.1074/jbc.M011311200 . free .
• Zhu CC, Cook LB, Hinkle PM . Dimerization and phosphorylation of thyrotropin-releasing hormone receptors are modulated by agonist stimulation . The Journal of Biological Chemistry . 277 . 31 . 28228–37 . August 2002 . 12023974 . 10.1074/jbc.M204221200 . free .
• Hanyaloglu AC, Seeber RM, Kohout TA, Lefkowitz RJ, Eidne KA . Homo- and hetero-oligomerization of thyrotropin-releasing hormone (TRH) receptor subtypes. Differential regulation of beta-arrestins 1 and 2 . The Journal of Biological Chemistry . 277 . 52 . 50422–30 . December 2002 . 12393857 . 10.1074/jbc.M209340200 . free.
• Cook LB, Zhu CC, Hinkle PM . Thyrotropin-releasing hormone receptor processing: role of ubiquitination and proteasomal degradation . Molecular Endocrinology . 17 . 9 . 1777–91 . September 2003 . 12805411 . 10.1210/me.2003-0073 . free .
• Igarashi-Migitaka J, Yamada S, Hara M, Sano T, Ozawa Y, Ohtani-Kaneko R, Hirata K . 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 . Endocrine Journal . 50 . 4 . 459–67 . August 2003 . 14599121 . 10.1507/endocrj.50.459 . free .
• Cook LB, Hinkle PM . Fate of internalized thyrotropin-releasing hormone receptors monitored with a timer fusion protein . Endocrinology . 145 . 7 . 3095–100 . July 2004 . 15117874 . 10.1210/en.2004-0304 . free .

External links

• Web site: Thyrotropin-Releasing Hormone Receptors . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2007-10-25 . 2012-09-08 . https://web.archive.org/web/20120908005215/http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1356 . dead .

Notes and References

1. Yamada M, Monden T, Konaka S, Mori M . Assignment of human thyrotropin-releasing hormone (TRH) receptor gene to chromosome 8 . Somatic Cell and Molecular Genetics . 19 . 6 . 577–80 . November 1993 . 8128317 . 10.1007/BF01233384 . 44982871 .
2. Book: Gershengorn MC . Thyrotropin-releasing hormone receptor: Cloning and regulation of its expression . Recent Progress in Hormone Research . 48 . 341–63 . 1993 . 8382829 . 10.1016/B978-0-12-571148-7.50016-6. 9780125711487 .