Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Follicle Stimulating Hormone Receptor (FSHR)

  • Masafumi TetsukaEmail author
  • Motozumi Matsui
  • Takashi Shimizu
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_585


Historical Background

Although the importance of follicle-stimulating hormone (FSH) in the reproduction has been well recognized for many years, FSH receptor (FSHR) had not been identified until 1970. High-affinity, low-capacity binding sites for FSH were demonstrated in 1972 using rat testicular tubules incubated with radiolabeled FSH (Simoni et al. 1997). In the following years, FSHR was identified, isolated, and purified in several species and cellular localization, ligand-receptor interaction, and intracellular signaling were studied extensively. FSHR gene was cloned in 1990 by screening rat Sertoli cell cDNA library. Since then, FSHR/Fshr has been cloned in several species ranging from human to reptile (Simoni et al. 1997). These findings led to identification of FSHR mutations and polymorphisms that either enhance (activating or gain-of-function mutation) or impair (inactivating or loss-of-function mutation) the function of the receptor (Lussiana...

This is a preview of subscription content, log in to check access.


  1. Araujo VR, Gastal MO, Figueiredo JR, Gastal EL. In vitro culture of bovine preantral follicles: a review. Reprod Biol Endocrinol. 2014;12:78.  https://doi.org/10.1186/1477-7827-12-78.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Arey BJ, Lopez FJ. Are circulating gonadotropin isoforms naturally occurring biased agonists? Basic and therapeutic implications. Rev Endocr Metab Disord. 2011;12:275–88.  https://doi.org/10.1007/s11154-011-9188-y.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Ayoub MA, Landomiel F, Gallay N, Jegot G, Poupon A, Crepieux P, Reiter E. Assessing gonadotropin receptor function by resonance energy transfer-based assays. Front Endocrinol (Lausanne). 2015;6:130.  https://doi.org/10.3389/fendo.2015.00130.CrossRefGoogle Scholar
  4. Banerjee AA, Mahale SD. Role of the extracellular and intracellular loops of follicle-stimulating hormone receptor in its function. Front Endocrinol (Lausanne). 2015;6:110.  https://doi.org/10.3389/fendo.2015.00110.CrossRefGoogle Scholar
  5. Bose CK. Follicle stimulating hormone receptor in ovarian surface epithelium and epithelial ovarian cancer. Oncol Res. 2008;17:231–8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18980020CrossRefGoogle Scholar
  6. Davis JS, Kumar TR, May JV, Bousfield GR. Naturally occurring follicle-stimulating hormone glycosylation variants. J Glycomics Lipidomics. 2014;4:e117.  https://doi.org/10.4172/2153-0637.1000e117.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Desai SS, Roy BS, Mahale SD. Mutations and polymorphisms in fsh receptor: functional implications in human reproduction. Reproduction. 2013;146:R235–48.  https://doi.org/10.1530/REP-13-0351.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Feng X, Zhang M, Guan R, Segaloff DL. Heterodimerization between the lutropin and follitropin receptors is associated with an attenuation of hormone-dependent signaling. Endocrinology. 2013;154:3925–30.  https://doi.org/10.1210/en.2013-1407.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Gartrell BA, Tsao CK, Galsky MD. The follicle-stimulating hormone receptor: a novel target in genitourinary malignancies. Urol Oncol. 2013;31:1403–7.  https://doi.org/10.1016/j.urolonc.2012.03.005.CrossRefPubMedPubMedCentralGoogle Scholar
  10. George JW, Dille EA, Heckert LL. Current concepts of follicle-stimulating hormone receptor gene regulation. Biol Reprod. 2011;84:7–17.  https://doi.org/10.1095/biolreprod.110.085043.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Ginther OJ. The theory of follicle selection in cattle. Domest Anim Endocrinol. 2016;57:85–99.  https://doi.org/10.1016/j.domaniend.2016.06.002.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Gloaguen P, Crepieux P, Heitzler D, Poupon A, Reiter E. Mapping the follicle-stimulating hormone-induced signaling networks. Front Endocrinol (Lausanne). 2011;2:45.  https://doi.org/10.3389/fendo.2011.00045.CrossRefGoogle Scholar
  13. Hermann BP, Heckert LL. Transcriptional regulation of the fsh receptor: new perspectives. Mol Cell Endocrinol. 2007;260–262:100–8.  https://doi.org/10.1016/j.mce.2006.09.005.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Jiang X, Dias JA, He X. Structural biology of glycoprotein hormones and their receptors: insights to signaling. Mol Cell Endocrinol. 2014;382:424–51.  https://doi.org/10.1016/j.mce.2013.08.021.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Kang DS, Tian X, Benovic JL. Role of beta-arrestins and arrestin domain-containing proteins in G protein-coupled receptor trafficking. Curr Opin Cell Biol. 2014;27:63–71.  https://doi.org/10.1016/j.ceb.2013.11.005.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Kumar TR. What have we learned about gonadotropin function from gonadotropin subunit and receptor knockout mice? Reproduction. 2005;130:293–302.  https://doi.org/10.1530/rep.1.00660. [pii] 130/3/2 93.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Kumar TR. Extragonadal fsh receptor: is it real? Biol Reprod. 2014;91:99.  https://doi.org/10.1095/biolreprod.114.124222.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Landomiel F, Gallay N, Jegot G, Tranchant T, Durand G, Bourquard T, Crepieux P, Poupon A, Reiter E. Biased signalling in follicle stimulating hormone action. Mol Cell Endocrinol. 2014;382:452–9.  https://doi.org/10.1016/j.mce.2013.09.035.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Lussiana C, Guani B, Mari C, Restagno G, Massobrio M, Revelli A. Mutations and polymorphisms of the fsh receptor (fshr) gene: clinical implications in female fecundity and molecular biology of fshr protein and gene. Obstet Gynecol Surv. 2008;63:785–95.  https://doi.org/10.1097/OGX.0b013e31818957eb. [pii] 0006254-200812000-00021.CrossRefPubMedPubMedCentralGoogle Scholar
  20. McGee EA, Raj RS. Regulators of ovarian preantral follicle development. Semin Reprod Med. 2015;33:179–84.  https://doi.org/10.1055/s-0035-1552584.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Minegishi T. Regulation of gonadotropin receptor in ovary. In: Leung PCK, Adashi EY, editors. The ovary. 2nd ed. San Diego: Elsevier Academic Press; 2004. p. 79–92.CrossRefGoogle Scholar
  22. Nataraja SG, Yu HN, Palmer SS. Discovery and development of small molecule allosteric modulators of glycoprotein hormone receptors. Front Endocrinol (Lausanne). 2015;6:142.  https://doi.org/10.3389/fendo.2015.00142.
  23. Papadimitriou K, Kountourakis P, Kottorou AE, Antonacopoulou AG, Rolfo C, Peeters M, Kalofonos HP. Follicle-stimulating hormone receptor (fshr): a promising tool in oncology? Mol Diagn Ther. 2016;20:523–30.  https://doi.org/10.1007/s40291-016-0218-z.CrossRefGoogle Scholar
  24. Ramaswamy S, Weinbauer GF. Endocrine control of spermatogenesis: role of fsh and lh/ testosterone. Spermatogenesis. 2014;4:e996025.  https://doi.org/10.1080/21565562.2014.996025.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Shenoy SK, Lefkowitz RJ. Beta-arrestin-mediated receptor trafficking and signal transduction. Trends Pharmacol Sci. 2011;32:521–33.  https://doi.org/10.1016/j.tips.2011.05.002.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Siegel ET, Kim HG, Nishimoto HK, Layman LC. The molecular basis of impaired follicle-stimulating hormone action: evidence from human mutations and mouse models. Reprod Sci. 2013;20:211–33.  https://doi.org/10.1177/1933719112461184.CrossRefPubMedPubMedCentralGoogle Scholar
  27. Simoni M, Casarini L. Mechanisms in endocrinology: genetics of fsh action: a 2014-and-beyond view. Eur J Endocrinol. 2014;170:R91–107.  https://doi.org/10.1530/EJE-13-0624.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Simoni M, Gromoll J, Nieschlag E. The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology. Endocr Rev. 1997;18:739–73 .http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9408742PubMedPubMedCentralGoogle Scholar
  29. Ulloa-Aguirre A, Zarinan T, Pasapera AM, Casas-Gonzalez P, Dias JA. Multiple facets of follicle-stimulating hormone receptor function. Endocrine. 2007;32:251–63.  https://doi.org/10.1007/s12020-008-9041-6.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Ulloa-Aguirre A, Zarinan T. The follitropin receptor: matching structure and function. Mol Pharmacol. 2016;90:596–608.  https://doi.org/10.1124/mol.116.104398.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Ulloa-Aguirre A, Crepieux P, Poupon A, Maurel MC, Reiter E. Novel pathways in gonadotropin receptor signaling and biased agonism. Rev Endocr Metab Disord. 2011;12:259–74.  https://doi.org/10.1007/s11154-011-9176-2.CrossRefPubMedPubMedCentralGoogle Scholar
  32. UniProtKB/Swiss-Prot. P23945 (FSHR_HUMAN). 2016. http://www.uniprot.org/uniprot/P23945. Accessed 1 Oct 2016.
  33. Vassart G, Pardo L, Costagliola S. A molecular dissection of the glycoprotein hormone receptors. Trends Biochem Sci. 2004;29:119–26.  https://doi.org/10.1016/j.tibs.2004.01.006. [pii] S0968000404000234.CrossRefPubMedPubMedCentralGoogle Scholar
  34. Wang J, Zhang W, Yu C, Zhang X, Zhang H, Guan Q, Zhao J, Xu J. Follicle-stimulating hormone increases the risk of postmenopausal osteoporosis by stimulating osteoclast differentiation. PLoS One. 2015;10:e0134986.  https://doi.org/10.1371/journal.pone.0134986.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Masafumi Tetsuka
    • 1
    Email author
  • Motozumi Matsui
    • 2
  • Takashi Shimizu
    • 3
  1. 1.Department of Agricultural and Life ScienceObihiro University of Agriculture and Veterinary MedicineObihiroJapan
  2. 2.Department of Clinical Veterinary ScienceObihiro University of Agriculture and Veterinary MedicineObihiroJapan
  3. 3.Graduate School of Animal and Food HygieneObihiro University of Agriculture and Veterinary MedicineObihiroJapan