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14-September-2008 18:02:43 - hormone receptor Gonadotropin-releasing hormone receptor Identifiers Symbol GNRHR Alt. Symbols GnRH-R; LRHR; Entrez 2798 HUGO 4421 OMIM 138850 RefSeq NM_000406 UniProt P30968 Other data Locus Chr. 4 q21.2 Gonadotropin-releasing hormone type 2 receptor 2 Identifiers Symbol GNRHR2 Entrez 114814 HUGO 16341 RefSeq NR_002328 UniProt Q96P88 Other data Locus Chr. 1 q12 The gonadotropin-releasing hormone receptor GNRHR, also known as the luteinizing hormone releasing hormone receptor LHRHR, is a member of the seven-transmembrane, G-protein coupled receptor GPCR family. It is expressed on the surface of pituitary gonadotrope cells as well as lymphocytes, breast, ovary, and prostate. This receptor is a 60 kDa G protein-coupled receptor and resides primarily in the pituitary and is responsible for eliciting the actions of LHRH after its release from the hypothalamus.1 Upon activation, the LHRHr stimulates tyrosine phosphatase and elicits the release of LH from the pituitary. Evidence exists showing the presence of LHRH and its receptor in extrapituitary tissues as well as a role in progression of some cancers.2 Contents 1 Function 2 Gene 3 Regulation 4 Clinical implications 5 References 6 External links Function Following binding of Gonadotropin releasing hormone GNRH, GNRHR associates with G-proteins that activate a phosphatidylinositol PtdIns-calcium second messenger system. Activation of GNRHR ultimately causes the release of follicle stimulating hormone FSH and luteinizing hormone LH. Gene There are two major forms of the GNRHR, each encoded by a separate receptor GNRHR, GNRHR2.34 Alternative splicing of the GNRHR gene, GNRHR, results in multiple transcript variants encoding different isoforms. More than 18 transcription initiation sites in the 5' region and multiple polyA signals in the 3' region have been identified for GNRHR. Regulation The GNRHR responds to GNRH as well as to synthetic GNRH agonists. Agonists stimulate the receptor, however prolonged exposure leads to a downregulation effect resulting in hypogonadism, an effect that is often medically utilized. GNRH antagonists block the receptor and inhibit gonadotropin release. GNRHRs are further regulated by the presence of sex hormones, inhibin, and activin. Clinical implications Defects in the GNRHR are a cause of hypogonadotropic hypogonadism HH.5 References ^ Millar RP 2005. GnRHs and GnRH receptors. Anim. Reprod. Sci. 88 1-2: 5-28. doi:10.1016/j.anireprosci.2005.05.032. PMID 16140177. ^ Harrison GS, Wierman ME, Nett TM, Glode LM 2004. Gonadotropin-releasing hormone and its receptor in normal and malignant cells. Endocr. Relat. Cancer 11 4: 725-48. doi:10.1677/erc.1.00777. PMID 15613448. ^ Neill JD, Musgrove LC, Duck LW 2004. Newly recognized GnRH receptors: function and relative role. Trends Endocrinol. Metab. 15 8: 383-92. doi:10.1016/j.tem.2004.08.005. PMID 15380810. ^ Cheng CK, Leung PC 2005. Molecular biology of gonadotropin-releasing hormone GnRH-I, GnRH-II, and their receptors in humans. Endocr. Rev. 26 2: 283-306. doi:10.1210/er.2003-0039. PMID 15561800. ^ Layman LC 2007. Hypogonadotropic hypogonadism. Endocrinol. Metab. Clin. North Am. 36 2: 283-96. doi:10.1016/j.ecl.2007.03.010. PMID 17543719. External links IUPHAR GPCR Database - GnRH receptor MeSH GNRHR+protein,+human v d e Transmembrane receptor: G protein-coupled receptors Class A: Rhodopsin like Adrenergic α1 A, B, D, α2 A, B, C, β1, β2, β3 Eicosanoid CysLT 1, 2, LTB4 1, 2, FPRL1, OXE, Prostaglandin DP, EP 1, 2, 3, 4, PGF, Prostacyclin, Thromboxane Neuropeptide B/W 1, 2, FF 1, 2, S, Y 1, 2, 4, 5 Orphan GPR 1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 79, 82, 83, 84, 85, 87, 88, 92, 101, 103, 119, 120, 132, 135, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 172, 173, 174, 176, 177, 182 Purinergics Adenosine A1, A2a, A2b, A3, P2Y, 1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14 Serotonin all but 5-HT3 5-HT1 A, B, D, E, F, 5-HT2 A, B, C, 5-HT 4, 5A, 6, 7 Other Acetylcholine M1, M2, M3, M4, M5 - Adrenomedullin - Anaphylatoxin C3a, C5a - Angiotensin 1, 2 - Apelin - Bile acid - Bombesin BRS3, GRPR, NMBR - Bradykinin B1, B2 - Cannabinoid CB1, CB2 - Chemokine - Cholecystokinin A, B - Dopamine D1, D2, D3, D4, D5 - EBI2 - Endothelin A, B - Estrogen - Formyl peptide 1, L1, L2 - Free fatty acid 1, 2, 3, 4 - FSH - Galanin 1, 2, 3 - Gonadotropin-releasing hormone 1, 2 - Ghrelin - Histamine H1, H2, H3, H4 - Kisspeptin - Luteinizing hormone/choriogonadotropin - Lysophospholipid 1, 2, 3, 4, 5, 6, 7, 8 - MAS 1, 1L, D, E, F, G, X1, X2, X3, X4 - Melanocortin 1, 2, 3, 4, 5 - MCHR 1, 2 - Melatonin 1A, 1B- Motilin - neuromedin B, U 1, 2 - Neurotensin 1, 2 - Opioid Delta, Kappa, Mu, Nociceptin, but not Sigma - Olfactory - Opsin 3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH - Orexin 1, 2 - Oxytocin - Oxoglutarate - PAF - Prokineticin 1, 2 - Prolactin-releasing peptide - Protease-activated 1, 2, 3, 4 - Relaxin 1, 2, 3, 4 - Somatostatin 1, 2, 3, 4, 5 - SREB - Succinate - TAAR 1, 2, 3, 5, 6, 8, 9 - Tachykinin 1, 2, 3 - Thyrotropin - Thyrotropin-releasing hormone - Urotensin-II - Vasopressin 1A, 1B, 2 Class B: Secretin like Brain-specific angiogenesis inhibitor 1, 2, 3 - Cadherin 1, 2, 3 - Calcitonin - CD97 - Corticotropin-releasing hormone 1, 2 - EMR 1, 2, 3 - Glucagon GR, GIPR, GLP1R, GLP2R - Growth hormone releasing hormone - PACAPR1- GPR 56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 157 - Latrophilin 1, 2, 3, ELTD1 - Parathyroid hormone 1, 2 - Secretin - Vasoactive intestinal peptide 1, 2 Class C: Metabotropic glutamate / pheromone Calcium-sensing receptor - GABA B 1, 2 - Glutamate receptor Metabotropic glutamate 1, 2, 3, 4, 5, 6, 7, 8 - GPRC6A - GPR 156, 158, 179 - RAIG 1, 2, 3, 4 - Taste receptors TAS1R 1, 2, 3 TAS2R 1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 38, 39, 40, 41, 43, 44, 45, 46, 47, 48, 49, 50 Frizzled / Smoothened Frizzled 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 - Smoothened v d e Neuropeptide receptors Hypothalamic hormone receptors CRH - FSH - LHRH - TRH - Somatostatin Pituitary hormone receptors Vasopressin 1A, 1B, 2 - Oxytocin - LHCG - Type I cytokine receptor GH, Prolactin - TSH Other hormone receptors Atrial natriuretic factor - Calcitonin - Cholecystokinin A, B - VIP Opioid receptors Delta - Kappa - Mu - Sigma 1, 2 - Nociceptin Other neuropeptide receptors Angiotensin - Bradykinin B1, B2 / Tachykinin TACR1 - Calcitonin gene-related peptide - Galanin - GPCR neuropeptide B/W, FF, S, Y - Neurotensin v d e Sex hormones and related agents primarily G03, also L02, H01C - human endogenous in CAPS Progestogens: receptor Agonist PROGESTERONE, Dienogest, Desogestrel, Drospirenone, Dydrogesterone, Ethisterone, Etonogestrel, Ethynodiol diacetate, Gestodene, Gestonorone, Levonorgestrel, Lynestrenol, Medroxyprogesterone, Megestrol, Norelgestromin, Norethisterone, Norethynodrel, Norgestimate, Norgestrel, Norgestrienone, Tibolone SPRM Asoprisnil, CDB-4124 Antiprogestogen Mifepristone Androgens: receptor Agonist TESTOSTERONE, Androstanolone, Fluoxymesterone, Mesterolone, Methyltestosterone, see also anabolic steroids Antiandrogen Bicalutamide, Cyproterone, Dienogest, Flutamide, Nilutamide, Spironolactone Estrogens: receptor Agonist ESTRADIOL, ESTRIOL, ESTRONE, Chlorotrianisene, Dienestrol, Diethylstilbestrol, Ethinylestradiol, Fosfestrol, Mestranol, Polyestradiol phosphate SERM Afimoxifene, Arzoxifene, Bazedoxifene, Clomifene, Fulvestrant, Lasofoxifene, Raloxifene, Tamoxifen, Toremifene AI Aminoglutethimide, Anastrozole, Atamestane, Exemestane, Fadrozole, Formestane, Letrozole, Vorozole Antiestrogen Mepitiostane Gonadotropins: FSHR/LHCGR ovulation stim. Clomifene, Urofollitropin Antigonadotropin Danazol, Gestrinone GnRH: receptor Agonist Buserelin, Goserelin, Histrelin, Leuprorelin, Nafarelin, Triptorelin Antagonist Abarelix, Cetrorelix, Ganirelix Retrieved from http://en..org/wiki/Gonadotropin-releasing_hormone_receptor Categories: Genes on chromosome 4 | Genes on chromosome 1 | Cell signaling | Signal transduction | G protein coupled receptorsHidden category: Protein pages needing a picture Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page This page was last modified on 19 December 2007, at 15:37
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