8i2h

Structural highlights

Disease

FSHR_HUMAN Defects in FSHR are a cause of ovarian dysgenesis type 1 (ODG1) [MIM:233300; also known as premature ovarian failure or gonadal dysgenesis XX type or XX gonadal dysgenesis (XXGD) or hereditary hypergonadotropic ovarian failure or hypergonadotropic ovarian dysgenesis with normal karyotype. ODG1 is an autosomal recessive disease characterized by primary amenorrhea, variable development of secondary sex characteristics, and high serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).^{[1] [2] [3] [4] [5] [6] [7]} Defects in FSHR are a cause of ovarian hyperstimulation syndrome (OHSS) [MIM:608115. OHSS is a disorder which occurs either spontaneously or most often as an iatrogenic complication of ovarian stimulation treatments for in vitro fertilization. The clinical manifestations vary from abdominal distention and discomfort to potentially life-threatening, massive ovarian enlargement and capillary leak with fluid sequestration. Pathologic features of this syndrome include the presence of multiple serous and hemorrhagic follicular cysts lined by luteinized cells, a condition called hyperreactio luteinalis.^{[8] [9] [10] [11] [12]}

Function

FSHR_HUMAN Receptor for follicle-stimulating hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.

References

1. ↑ Aittomaki K, Lucena JL, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, Kaskikari R, Sankila EM, Lehvaslaiho H, Engel AR, Nieschlag E, Huhtaniemi I, de la Chapelle A. Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell. 1995 Sep 22;82(6):959-68. PMID:7553856
2. ↑ Jiang M, Aittomaki K, Nilsson C, Pakarinen P, Iitia A, Torresani T, Simonsen H, Goh V, Pettersson K, de la Chapelle A, Huhtaniemi I. The frequency of an inactivating point mutation (566C-->T) of the human follicle-stimulating hormone receptor gene in four populations using allele-specific hybridization and time-resolved fluorometry. J Clin Endocrinol Metab. 1998 Dec;83(12):4338-43. PMID:9851774
3. ↑ Beau I, Touraine P, Meduri G, Gougeon A, Desroches A, Matuchansky C, Milgrom E, Kuttenn F, Misrahi M. A novel phenotype related to partial loss of function mutations of the follicle stimulating hormone receptor. J Clin Invest. 1998 Oct 1;102(7):1352-9. PMID:9769327 doi:10.1172/JCI3795
4. ↑ Touraine P, Beau I, Gougeon A, Meduri G, Desroches A, Pichard C, Detoeuf M, Paniel B, Prieur M, Zorn JR, Milgrom E, Kuttenn F, Misrahi M. New natural inactivating mutations of the follicle-stimulating hormone receptor: correlations between receptor function and phenotype. Mol Endocrinol. 1999 Nov;13(11):1844-54. PMID:10551778
5. ↑ Doherty E, Pakarinen P, Tiitinen A, Kiilavuori A, Huhtaniemi I, Forrest S, Aittomaki K. A Novel mutation in the FSH receptor inhibiting signal transduction and causing primary ovarian failure. J Clin Endocrinol Metab. 2002 Mar;87(3):1151-5. PMID:11889179
6. ↑ Allen LA, Achermann JC, Pakarinen P, Kotlar TJ, Huhtaniemi IT, Jameson JL, Cheetham TD, Ball SG. A novel loss of function mutation in exon 10 of the FSH receptor gene causing hypergonadotrophic hypogonadism: clinical and molecular characteristics. Hum Reprod. 2003 Feb;18(2):251-6. PMID:12571157
7. ↑ Meduri G, Touraine P, Beau I, Lahuna O, Desroches A, Vacher-Lavenu MC, Kuttenn F, Misrahi M. Delayed puberty and primary amenorrhea associated with a novel mutation of the human follicle-stimulating hormone receptor: clinical, histological, and molecular studies. J Clin Endocrinol Metab. 2003 Aug;88(8):3491-8. PMID:12915623
8. ↑ Vasseur C, Rodien P, Beau I, Desroches A, Gerard C, de Poncheville L, Chaplot S, Savagner F, Croue A, Mathieu E, Lahlou N, Descamps P, Misrahi M. A chorionic gonadotropin-sensitive mutation in the follicle-stimulating hormone receptor as a cause of familial gestational spontaneous ovarian hyperstimulation syndrome. N Engl J Med. 2003 Aug 21;349(8):753-9. PMID:12930927 doi:http://dx.doi.org/10.1056/NEJMoa030065
9. ↑ Smits G, Olatunbosun O, Delbaere A, Pierson R, Vassart G, Costagliola S. Ovarian hyperstimulation syndrome due to a mutation in the follicle-stimulating hormone receptor. N Engl J Med. 2003 Aug 21;349(8):760-6. PMID:12930928 doi:http://dx.doi.org/10.1056/NEJMoa030064
10. ↑ Montanelli L, Delbaere A, Di Carlo C, Nappi C, Smits G, Vassart G, Costagliola S. A mutation in the follicle-stimulating hormone receptor as a cause of familial spontaneous ovarian hyperstimulation syndrome. J Clin Endocrinol Metab. 2004 Apr;89(4):1255-8. PMID:15080154
11. ↑ De Leener A, Montanelli L, Van Durme J, Chae H, Smits G, Vassart G, Costagliola S. Presence and absence of follicle-stimulating hormone receptor mutations provide some insights into spontaneous ovarian hyperstimulation syndrome physiopathology. J Clin Endocrinol Metab. 2006 Feb;91(2):555-62. Epub 2005 Nov 8. PMID:16278261 doi:jc.2005-1580
12. ↑ De Leener A, Caltabiano G, Erkan S, Idil M, Vassart G, Pardo L, Costagliola S. Identification of the first germline mutation in the extracellular domain of the follitropin receptor responsible for spontaneous ovarian hyperstimulation syndrome. Hum Mutat. 2008 Jan;29(1):91-8. PMID:17721928 doi:10.1002/humu.20604
13. ↑ Duan J, Xu P, Zhang H, Luan X, Yang J, He X, Mao C, Shen DD, Ji Y, Cheng X, Jiang H, Jiang Y, Zhang S, Zhang Y, Xu HE. Mechanism of hormone and allosteric agonist mediated activation of follicle stimulating hormone receptor. Nat Commun. 2023 Jan 31;14(1):519. PMID:36720854 doi:10.1038/s41467-023-36170-3