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Gene Review

Fshr  -  follicle stimulating hormone receptor

Rattus norvegicus

Synonyms: FSH-R, Follicle-stimulating hormone receptor, Follitropin receptor
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Disease relevance of Fshr


High impact information on Fshr


Chemical compound and disease context of Fshr


Biological context of Fshr

  • Identification of the sites of N-linked glycosylation on the follicle-stimulating hormone (FSH) receptor and assessment of their role in FSH receptor function [9].
  • The FSHR gene contained 10 exons and nine introns [10].
  • Comparison of the FSHR gene to the LH receptor gene revealed a number of striking similarities which clearly indicate that these receptors evolved through gene duplication [10].
  • Comparison of the sequences of the extracellular domains (ECD) of the receptors reveals two regions (amino acids 4-56 and 265-319 in FSH-R) that share relatively little amino acid sequence similarity [11].
  • Fshr rats, however, exhibited a circadian pattern (P less than 0.02) only with regard to water consumption under an LD 12:12 lighting schedule; they did not exhibit circadian patterns of drinking water (P less than 0.054) in DD or ethanol in LD (P less than 0.24) or in DD (P less than 0.67) conditions [12].

Anatomical context of Fshr


Associations of Fshr with chemical compounds

  • The selectivity for FSH is attested by the fact that the related human glycoprotein hormones human CG and human TSH do not stimulate adenylyl cyclase in FSH-R expressing cells even when these hormones are present at high concentrations [18].
  • Voluntary drinking responses to an alternating three-bottle, two-choice paradigm to tap water or to 5% ethanol were measured in adult male Fisher (Fshr; N = 14) and spontaneously hypertensive (SP; N = 16) rats for 6-9 days [12].
  • Estradiol also enhanced the extent of LH and FSH receptor formation by other cAMP-inducing ligands, including FSH, prostaglandin E2, and forskolin [19].
  • Although cortisol and dexamethasone increased choleragen-induced cAMP accumulation, only cortisol elevated LH receptors, and dexamethasone inhibited FSH receptor formation [19].
  • However, when eLH was assayed in the eCG-primed cells, it did show stimulating activity with respect to the production of plasminogen activator and progesterone; however, the dose-response curves were not parallel to those of eFSH and eCG. eCG had much less FSH receptor-binding activity (0.29 X NIH FSH-S13) than eLH [20].

Regulatory relationships of Fshr


Other interactions of Fshr

  • At 21 days of age data showed that FSH-R mRNA levels were significantly higher in both hyper- and hypothyroid rat testes compared to controls, but no differences were detected in recovered 50-day-old rats [25].
  • These results suggested that androgens regulate granulosa cell aromatase activity not only as substrates, but also by acting at a site before cAMP production (possibly at the level of the FSH receptor) in the control of FSH-induced enzyme activity [26].
  • Interestingly, BMP-15 severely reduced the levels of FSH receptor mRNA in both basal and FSH-stimulated cells [22].
  • As assumed, BMP-6 did not alter basal FSH-R mRNA levels, whereas it inhibited FSH- and forskolin- but not 8-bromo-cAMP-induced FSH-R mRNA accumulation [7].
  • Moreover, TNF-alpha impairs the LH receptor formation induced by forskolin, cholera toxin or 8-Bromo-cAMP, indicating that the cytokine also acts at a step distal to FSH receptor and to cAMP formation [27].

Analytical, diagnostic and therapeutic context of Fshr


  1. Heat stress diminishes gonadotropin receptor expression and enhances susceptibility to apoptosis of rat granulosa cells. Shimizu, T., Ohshima, I., Ozawa, M., Takahashi, S., Tajima, A., Shiota, M., Miyazaki, H., Kanai, Y. Reproduction (2005) [Pubmed]
  2. The relationship between 3',5'-cyclic adenosine monophosphate and calcium in mediating follicle-stimulating hormone signal transduction in Sertoli cells. Gorczynska, E., Spaliviero, J., Handelsman, D.J. Endocrinology (1994) [Pubmed]
  3. Maintenance of in vitro granulosa cell function by adenoviral mediated follicle stimulating hormone receptor gene transduction. Serikawa, T., Fujita, K., Nagata, H., Oite, T., Tanaka, K. J. Assist. Reprod. Genet. (2006) [Pubmed]
  4. Intratesticular steroids and gonadotrophin receptor concentrations in the testes of immature unilaterally cryptorchid rats. Bergh, A., Damber, J.E., Huhtaniemi, I. Int. J. Androl. (1987) [Pubmed]
  5. Pituitary follicle-stimulating hormone (FSH) induces CREM gene expression in Sertoli cells: involvement in long-term desensitization of the FSH receptor. Monaco, L., Foulkes, N.S., Sassone-Corsi, P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  6. Identification of a short linear sequence present in the C-terminal tail of the rat follitropin receptor that modulates arrestin-3 binding in a phosphorylation-independent fashion. Kishi, H., Krishnamurthy, H., Galet, C., Bhaskaran, R.S., Ascoli, M. J. Biol. Chem. (2002) [Pubmed]
  7. Biological function and cellular mechanism of bone morphogenetic protein-6 in the ovary. Otsuka, F., Moore, R.K., Shimasaki, S. J. Biol. Chem. (2001) [Pubmed]
  8. Follicle-stimulating hormone receptor-mediated uptake of 45Ca2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase. Grasso, P., Reichert, L.E. Endocrinology (1990) [Pubmed]
  9. Identification of the sites of N-linked glycosylation on the follicle-stimulating hormone (FSH) receptor and assessment of their role in FSH receptor function. Davis, D., Liu, X., Segaloff, D.L. Mol. Endocrinol. (1995) [Pubmed]
  10. Structural organization of the follicle-stimulating hormone receptor gene. Heckert, L.L., Daley, I.J., Griswold, M.D. Mol. Endocrinol. (1992) [Pubmed]
  11. Expression of extracellular domain peptides of the FSH receptor and their effect on receptor-ligand interactions in vitro. Sharma, S.C., Catterall, J.F. Mol. Cell. Endocrinol. (1995) [Pubmed]
  12. Strain differences in circadian drinking behaviors of ethanol and water in rats. Pasley, J.N., Powell, E.W., Halberg, F. Prog. Clin. Biol. Res. (1987) [Pubmed]
  13. Cellular localization and hormonal regulation of follicle-stimulating hormone and luteinizing hormone receptor messenger RNAs in the rat ovary. Camp, T.A., Rahal, J.O., Mayo, K.E. Mol. Endocrinol. (1991) [Pubmed]
  14. Effects of removal of carboxy-terminal extension from equine luteinizing hormone (LH) beta-subunit on LH and follicle-stimulating hormone receptor-binding activities and LH steroidogenic activity in rat testicular Leydig cells. Bousfield, G.R., Liu, W.K., Ward, D.N. Endocrinology (1989) [Pubmed]
  15. Essential role of the oocyte in estrogen amplification of follicle-stimulating hormone signaling in granulosa cells. Otsuka, F., Moore, R.K., Wang, X., Sharma, S., Miyoshi, T., Shimasaki, S. Endocrinology (2005) [Pubmed]
  16. Decreased spermatogenesis as the result of an induced autoimmune reaction directed against the gonadotropin receptors in male rats. Graf, K.M., Dias, J.A., Griswold, M.D. J. Androl. (1997) [Pubmed]
  17. Properties of follitropin-receptor interaction. Characterization of the interaction of follitropin with receptors in purified membranes isolated from mature rat testes tubules. Abou-Issa, H., Reichert, L.E. J. Biol. Chem. (1976) [Pubmed]
  18. The testicular receptor for follicle stimulating hormone: structure and functional expression of cloned cDNA. Sprengel, R., Braun, T., Nikolics, K., Segaloff, D.L., Seeburg, P.H. Mol. Endocrinol. (1990) [Pubmed]
  19. Estrogens enhance the adenosine 3',5'-monophosphate-mediated induction of follicle-stimulating hormone and luteinizing hormone receptors in rat granulosa cells. Knecht, M., Darbon, J.M., Ranta, T., Baukal, A.J., Catt, K.J. Endocrinology (1984) [Pubmed]
  20. Priming procedure and hormone preparations influence rat granulosa cell response. Liu, W.K., Bousfield, G.R., Moore, W.T., Ward, D.N. Endocrinology (1985) [Pubmed]
  21. Transforming growth factor beta modulates gonadotropin receptor expression in porcine and rat granulosa cells differently. Gitay-Goren, H., Kim, I.C., Miggans, S.T., Schomberg, D.W. Biol. Reprod. (1993) [Pubmed]
  22. Bone morphogenetic protein-15 inhibits follicle-stimulating hormone (FSH) action by suppressing FSH receptor expression. Otsuka, F., Yamamoto, S., Erickson, G.F., Shimasaki, S. J. Biol. Chem. (2001) [Pubmed]
  23. Changes in ovarian luteinizing hormone and follicle-stimulating hormone receptor content and in gonadotropin-induced ornithine decarboxylase activity during prepubertal and pubertal development of the female rat. White, S.S., Ojeda, S.R. Endocrinology (1981) [Pubmed]
  24. Regulation of follicle-stimulating hormone receptor messenger ribonucleic acid levels in cultured rat granulosa cells. Minegishi, T., Tano, M., Nakamura, K., Karino, S., Miyamoto, K., Ibuki, Y. Mol. Cell. Endocrinol. (1995) [Pubmed]
  25. Effect of thyroid hormone on the development and gene expression of hormone receptors in rat testes in vivo. Rao, J.N., Liang, J.Y., Chakraborti, P., Feng, P. J. Endocrinol. Invest. (2003) [Pubmed]
  26. Site of action of androgens on follicle-stimulating hormone-induced aromatase activity in cultured rat granulosa cells. Daniel, S.A., Armstrong, D.T. Endocrinology (1984) [Pubmed]
  27. Tumor necrosis factor-alpha inhibits follicle-stimulating hormone-induced differentiation in cultured rat granulosa cells. Darbon, J.M., Oury, F., Laredo, J., Bayard, F. Biochem. Biophys. Res. Commun. (1989) [Pubmed]
  28. A role for neurotransmitters in early follicular development: induction of functional follicle-stimulating hormone receptors in newly formed follicles of the rat ovary. Mayerhofer, A., Dissen, G.A., Costa, M.E., Ojeda, S.R. Endocrinology (1997) [Pubmed]
  29. Expression of follicle-stimulating hormone receptor mRNA in rat testes and Sertoli cells. Heckert, L.L., Griswold, M.D. Mol. Endocrinol. (1991) [Pubmed]
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