Glycoprotein hormone receptors
More information on this family may be found on the IUPHAR-DB family and introduction pages.
Glycoprotein hormone receptors (provisional nomenclature) are activated by a heterodimeric glycoprotein made up of a common α chain (116 amino-acid ENSG00000135346), with a unique β chain that confers the biological specificity to FSH (follicle-stimulating hormone, follitropin, 129 amino-acid, ENSG00000131808), LH (luteinizing hormone, lutropin, 141 amino-acid ENSG00000104826), hCG (choriogonadotropin, chorionic gonadotropin, 165 amino-acid, ENSG00000104818/ENSG00000104827) or TSH (thyrotropin, thyroid-stimulating hormone, 138 amino-acid ENSG00000134200). There is binding cross-reactivity across the endogenous agonists for each of the glycoprotein hormone receptors. The deglycosylated hormones appear to exhibit reduced efficacy at these receptors [14].
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Receptors 
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Chiamolera, MI; Wondisford, FE. (2009) Minireview: Thyrotropin-releasing hormone and the thyroid hormone feedback mechanism. Endocrinology, 150 (3): 1091-6. [PMID:19179434]
George, JW; Dille, EA; Heckert, LL. (2011) Current concepts of follicle-stimulating hormone receptor gene regulation. Biol. Reprod., 84 (1): 7-17. [PMID:20739665]
Hermann, BP; Heckert, LL. (2007) Transcriptional regulation of the FSH receptor: new perspectives. Mol. Cell. Endocrinol., 260-262: 100-8. [PMID:17084019]
Kleinau, G; Krause, G. (2009) Thyrotropin and homologous glycoprotein hormone receptors: structural and functional aspects of extracellular signaling mechanisms. Endocr. Rev., 30 (2): 133-51. [PMID:19176466]
Mueller, S; Jaeschke, H; Günther, R; Paschke, R. (2010) The hinge region: an important receptor component for GPHR function. Trends Endocrinol. Metab., 21 (2): 111-22. [PMID:19819720]
Piersma, D; Verhoef-Post, M; Berns, EM; Themmen, AP. (2007) LH receptor gene mutations and polymorphisms: an overview. Mol. Cell. Endocrinol., 260-262: 282-6. [PMID:17030087]
Puett, D; Angelova, K; da Costa, MR; Warrenfeltz, SW; Fanelli, F. (2010) The luteinizing hormone receptor: insights into structure-function relationships and hormone-receptor-mediated changes in gene expression in ovarian cancer cells. Mol. Cell. Endocrinol., 329 (1-2): 47-55. [PMID:20444430]
Rao, CV; Lei, ZM. (2007) The past, present and future of nongonadal LH/hCG actions in reproductive biology and medicine. Mol. Cell. Endocrinol., 269 (1-2): 2-8. [PMID:17382462]
Ziecik, AJ; Kaczmarek, MM; Blitek, A; Kowalczyk, AE; Li, X; Rahman, NA. (2007) Novel biological and possible applicable roles of LH/hCG receptor. Mol. Cell. Endocrinol., 269 (1-2): 51-60. [PMID:17367919]
1. Aittomäki, K., Lucena, J. L., Pakarinen, P., Sistonen, P., Tapanainen, J., Gromoll, J., Kaskikari, R., Sankila, E. M., Lehväslaiho, H., Engel, A. R., Nieschlag, E., Huhtaniemi, I. and de la Chapelle, A. (1995) Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell, 82: 959-968. [PMID:7553856]
2. Beau, I., Touraine, P., Meduri, G., Gougeon, A., Desroches, A., Matuchansky, C., Milgrom, E., Kuttenn, F. and Misrahi, M. (1998) A novel phenotype related to partial loss of function mutations of the follicle stimulating hormone receptor. J Clin Invest, 102: 1352-1359. [PMID:9769327]
3. Gromoll, J; Simoni, M; Nieschlag, E. (1996) An activating mutation of the follicle-stimulating hormone receptor autonomously sustains spermatogenesis in a hypophysectomized man. J. Clin. Endocrinol. Metab., 81 (4): 1367-70. [PMID:8636335]
4. Jia, X. C., Oikawa, M., Bo, M., Tanaka, T., Ny, T., Boime, I. and Hsueh, A. J. (1991) Expression of human luteinizing hormone (LH) receptor: interaction with LH and chorionic gonadotropin from human but not equine, rat, and ovine species. Mol Endocrinol, 5: 759-768. [PMID:1922095]
5. Kopp, P; van Sande, J; Parma, J; Duprez, L; Gerber, H; Joss, E; Jameson, JL; Dumont, JE; Vassart, G. (1995) Brief report: congenital hyperthyroidism caused by a mutation in the thyrotropin-receptor gene. N. Engl. J. Med., 332 (3): 150-4. [PMID:7800007]
6. Latronico, AC; Segaloff, DL. (1999) Naturally occurring mutations of the luteinizing-hormone receptor: lessons learned about reproductive physiology and G protein-coupled receptors. Am. J. Hum. Genet., 65 (4): 949-58. [PMID:10486313]
7. Liu, G., Duranteau, L., Carel, J. C., Monroe, J., Doyle, D. A. and Shenker, A. (1999) Leydig-cell tumors caused by an activating mutation of the gene encoding the luteinizing hormone receptor. N Engl J Med, 341: 1731-1736. [PMID:10580072]
8. Müller, T., Gromoll, J. and Simoni, M. (2003) Absence of exon 10 of the human luteinizing hormone (LH) receptor impairs LH, but not human chorionic gonadotropin action. J Clin Endocrinol Metab, 88: 2242-2249. [PMID:12727981]
9. Nechamen, C. A. and Dias, J. A. (2003) Point mutations in follitropin receptor result in ER retention. Mol Cell Endocrinol, 201: 123-131. [PMID:12706300]
10. Palmer, S. S., Mckenna, S. and Arkinstall, S. (2005) Discovery of new molecules for the future treatment of infertility. Reproductive Biomedicine Online 10 Suppl (Proceedings: Gonadotropins from Basic Research to Clinical Practice; Munich Germany., : 45-54.
11. Parma, J., Duprez, L., Van Sande, J., Cochaux, P., Gervy, C., Mockel, J., Dumont, J. and Vassart, G. (1993) Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature, 365: 649-651. [PMID:8413627]
12. Quintana, J; Hipkin, RW; Sánchez-Yagüe, J; Ascoli, M. (1994) Follitropin (FSH) and a phorbol ester stimulate the phosphorylation of the FSH receptor in intact cells. J. Biol. Chem., 269 (12): 8772-9. [PMID:8132609]
13. Rapoport, B., Chazenbalk, G. D., Jaume, J. C. and McLachlan, S. M. (1998) The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies. Endocr Rev, 19: 673-716. [PMID:9861544]
14. Sairam, MR. (1989) Role of carbohydrates in glycoprotein hormone signal transduction. FASEB J., 3 (8): 1915-26. [PMID:2542111]
15. Shenker, A. (2002) Activating mutations of the lutropin choriogonadotropin receptor in precocious puberty. Receptors Channels, 8: 3-18. [PMID:12408104]
16. Sunthornthepvarakui, T; Gottschalk, ME; Hayashi, Y; Refetoff, S. (1995) Brief report: resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene. N. Engl. J. Med., 332 (3): 155-60. [PMID:7528344]
17. Touraine, P., Beau, I., Gougeon, A., Meduri, G., Desroches, A., Pichard, C., Detoeuf, M., Paniel, B., Prieur, M., Zorn, J. R., Milgrom, E., Kuttenn, F. and Misrahi, M. (1999) New natural inactivating mutations of the follicle-stimulating hormone receptor: correlations between receptor function and phenotype. Mol Endocrinol, 13: 1844-1854. [PMID:10551778]
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Animal follitropins are less potent than the human hormone as agonists at the human FSH receptor. Autoimmune antibodies that act as agonists of the TSH receptor are found in patients with Grave's disease (e.g. [13]). Gain- and loss-of-function mutations of the FSH receptor are associated with human reproductive disorders [1-3,17]. Loss-of-function mutations of the LH receptor are associated with Leydig cell hypoplasia and gain-of-function mutations are associated with male-limited gonadotropin-independent precocious puberty (e.g. [6,15]) and Leydig cell tumours [7]. Mutations of the TSH receptor exhibiting constitutive activity underlie hyperfunctioning thyroid adenomas [11] and congenital hyperthyroidism [5]. TSH receptor loss-of-function mutations are associated with TSH resistance [16]. The rat FSH receptor also stimulates phosphoinositide turnover through an unidentified G protein [12].