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Gene Review

Fshb  -  follicle stimulating hormone beta

Mus musculus

Synonyms: FSH, FSH-B, FSH-beta, Follicle-stimulating hormone beta subunit, Follitropin beta chain, ...
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Disease relevance of Fshb


High impact information on Fshb

  • Minimal data has been accumulated so far involving human mutations in the FSH beta, LH beta, or the gonadotropin receptor genes [6].
  • To generate animal models for human diseases involving the gonadotropin signal transduction pathway, we produced mice deficient in the FSH beta subunit and therefore in FSH using ES cell technology [6].
  • We recently found that mice deficient in the beta-subunit of follicle-stimulating hormone (FSHbeta) are protected from bone loss despite severe estrogen deficiency [7].
  • Here, we identify elements in the mouse FSHbeta promoter responsible for GnRH-mediated induction utilizing the LbetaT2 cell line that endogenously expresses FSH [8].
  • Transient transfection of each receptor, along with ligand treatment, stimulates the mouse FSHbeta promoter, but induction is severely diminished using receptors that lack the ability to bind DNA, indicating that induction is likely through direct DNA binding [9].

Biological context of Fshb


Anatomical context of Fshb


Associations of Fshb with chemical compounds

  • Production of the beta-subunit of FSH is the rate-limiting step in FSH synthesis, and a number of peptide and steroid hormones within the reproductive axis have been found to regulate transcription of the FSH beta-subunit gene [1].
  • To test this hypothesis, we used an LHbeta promoter to immortalize a cell that represents a subsequent stage of gonadotrope differentiation (expression of alpha-subunit, GnRH receptor, and LH beta-subunit but not FSH beta-subunit) [17].
  • FSHbeta primary transcript and mRNA levels were increased within 30-60 min, but these effects were blocked by preincubation with the transcription inhibitor actinomycin-D, suggesting that the FSHbeta gene is a direct target of the activin signal transduction cascade [15].
  • Thus, during GnRHA inhibition of endogenous GnRH activity, androgen uniquely stimulates FSH beta mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)[18]
  • Furthermore, the in vitro data indicate that the suppression of human FSH beta gene expression is at least partly a direct androgen effect that does not require aromatization of testosterone to estradiol [16].
  • Disruption of Smad binding to the promoter with a Smad protein lacking the DNA-binding domain or an FSHbeta promoter containing mutated activin-response elements prevents the synergistic enhancement of FSHbeta transcription [19].

Physical interactions of Fshb


Regulatory relationships of Fshb

  • Collectively, these data suggest that activins use both SMAD2- and SMAD3-dependent mechanisms to stimulate FSHbeta transcription in mouse gonadotrope cells [15].
  • We identify binding sites for the orphan nuclear receptor steroidogenic factor-1 and the heterotrimeric transcription factor nuclear factor Y and show that these elements functionally interact to regulate FSH beta gene expression in an L beta T2 cell-specific manner [20].
  • Daily injections of 1 microgram GnRH for 14 days induced expression of the human FSH beta gene in male and female mice [16].
  • These results suggest that TSH beta overexpression in TU-SPCs must be caused by a deprivation of TH which plays a role in the negative feedback system and that FSH beta expression also might be enhanced by mechanisms similar to those of TSH beta, probably due to certain overlapping of the endocrinological regulation of TSH and FSH in H. retardatus [21].

Other interactions of Fshb

  • TSH beta-subunit transcripts appear several days later but precede transcription of the GH and FSH beta and LH beta-subunit genes [22].
  • Regulation of FSHbeta and GnRH receptor gene expression in activin receptor II knockout male mice [23].
  • Compared to castrated wild-type (WT) mice, FSHbeta mRNA levels in the pituitaries of Acvr2 null mice were significantly downregulated in the absence of gonadal feedback [23].
  • Using RT-PCR, we show that these cells synthesize FSH beta- subunit messenger RNA, which is induced by activin and inhibited by follistatin [11].
  • Transient transfection of SMAD3, but not SMADs 1, 2, 4, 5, or 8, stimulated endogenous FSHbeta mRNA levels [15].

Analytical, diagnostic and therapeutic context of Fshb


  1. Activin and glucocorticoids synergistically activate follicle-stimulating hormone beta-subunit gene expression in the immortalized LbetaT2 gonadotrope cell line. McGillivray, S.M., Thackray, V.G., Coss, D., Mellon, P.L. Endocrinology (2007) [Pubmed]
  2. The gonadotropin-releasing hormone receptor gene promoter directs pituitary-specific oncogene expression in transgenic mice. Albarracin, C.T., Frosch, M.P., Chin, W.W. Endocrinology (1999) [Pubmed]
  3. Simian virus 40 T antigen-induced gonadotroph adenomas: a model of human null cell adenomas. Kumar, T.R., Graham, K.E., Asa, S.L., Low, M.J. Endocrinology (1998) [Pubmed]
  4. The follicle-stimulating hormone (FSH) beta- and common alpha-subunits are expressed in mouse testis, as determined in wild-type mice and those transgenic for the FSH beta-subunit/herpes simplex virus thymidine kinase fusion gene. Markkula, M., Hämäläinen, T., Loune, E., Huhtaniemi, I. Endocrinology (1995) [Pubmed]
  5. The Parkes lecture. Mutations of gonadotrophin and gonadotrophin receptor genes: what do they teach us about reproductive physiology? Huhtaniemi, I. J. Reprod. Fertil. (2000) [Pubmed]
  6. Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Kumar, T.R., Wang, Y., Lu, N., Matzuk, M.M. Nat. Genet. (1997) [Pubmed]
  7. Follicle-stimulating hormone stimulates TNF production from immune cells to enhance osteoblast and osteoclast formation. Iqbal, J., Sun, L., Kumar, T.R., Blair, H.C., Zaidi, M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. A novel AP-1 site is critical for maximal induction of the follicle-stimulating hormone beta gene by gonadotropin-releasing hormone. Coss, D., Jacobs, S.B., Bender, C.E., Mellon, P.L. J. Biol. Chem. (2004) [Pubmed]
  9. Androgens, progestins, and glucocorticoids induce follicle-stimulating hormone beta-subunit gene expression at the level of the gonadotrope. Thackray, V.G., McGillivray, S.M., Mellon, P.L. Mol. Endocrinol. (2006) [Pubmed]
  10. Analysis of ovarian gene expression in follicle-stimulating hormone beta knockout mice. Burns, K.H., Yan, C., Kumar, T.R., Matzuk, M.M. Endocrinology (2001) [Pubmed]
  11. Cell-specific transcriptional regulation of follicle-stimulating hormone-beta by activin and gonadotropin-releasing hormone in the LbetaT2 pituitary gonadotrope cell model. Pernasetti, F., Vasilyev, V.V., Rosenberg, S.B., Bailey, J.S., Huang, H.J., Miller, W.L., Mellon, P.L. Endocrinology (2001) [Pubmed]
  12. The promoter of the rat gonadotropin-releasing hormone receptor gene directs the expression of the human placental alkaline phosphatase reporter gene in gonadotrope cells in the anterior pituitary gland as well as in multiple extrapituitary tissues. Granger, A., Ngô-Muller, V., Bleux, C., Guigon, C., Pincas, H., Magre, S., Daegelen, D., Tixier-Vidal, A., Counis, R., Laverrière, J.N. Endocrinology (2004) [Pubmed]
  13. Characterization of integrin expression in the mouse ovary. Burns, K.H., Owens, G.E., Fernandez, J.M., Nilson, J.H., Matzuk, M.M. Biol. Reprod. (2002) [Pubmed]
  14. Bromodomain containing 2 (Brd2) is expressed in distinct patterns during ovarian folliculogenesis independent of FSH or GDF9 action. Trousdale, R.K., Wolgemuth, D.J. Mol. Reprod. Dev. (2004) [Pubmed]
  15. Both SMAD2 and SMAD3 mediate activin-stimulated expression of the follicle-stimulating hormone beta subunit in mouse gonadotrope cells. Bernard, D.J. Mol. Endocrinol. (2004) [Pubmed]
  16. Hormonal regulation of human follicle-stimulating hormone-beta subunit gene expression: GnRH stimulation and GnRH-independent androgen inhibition. Kumar, T.R., Low, M.J. Neuroendocrinology (1995) [Pubmed]
  17. Immortalization of pituitary cells at discrete stages of development by directed oncogenesis in transgenic mice. Alarid, E.T., Windle, J.J., Whyte, D.B., Mellon, P.L. Development (1996) [Pubmed]
  18. Androgen selectively stimulates follicle-stimulating hormone-beta mRNA levels after gonadotropin-releasing hormone antagonist administration. Wierman, M.E., Wang, C. Biol. Reprod. (1990) [Pubmed]
  19. Synergistic induction of follicle-stimulating hormone beta-subunit gene expression by gonadal steroid hormone receptors and Smad proteins. Thackray, V.G., Mellon, P.L. Endocrinology (2008) [Pubmed]
  20. Nuclear factor Y and steroidogenic factor 1 physically and functionally interact to contribute to cell-specific expression of the mouse Follicle-stimulating hormone-beta gene. Jacobs, S.B., Coss, D., McGillivray, S.M., Mellon, P.L. Mol. Endocrinol. (2003) [Pubmed]
  21. Spatio-temporal expression of TSH beta and FSH beta genes in normally metamorphosing, metamorphosed, and metamorphosis-arrested Hynobius retardatus. Kanki, K., Wakahara, M. Gen. Comp. Endocrinol. (2000) [Pubmed]
  22. Targeted ablation of cells in the pituitary primordia of transgenic mice. Burrows, H.L., Birkmeier, T.S., Seasholtz, A.F., Camper, S.A. Mol. Endocrinol. (1996) [Pubmed]
  23. Regulation of FSHbeta and GnRH receptor gene expression in activin receptor II knockout male mice. Kumar, T.R., Agno, J., Janovick, J.A., Conn, P.M., Matzuk, M.M. Mol. Cell. Endocrinol. (2003) [Pubmed]
  24. Luteinizing hormone deficiency and female infertility in mice lacking the transcription factor NGFI-A (Egr-1). Lee, S.L., Sadovsky, Y., Swirnoff, A.H., Polish, J.A., Goda, P., Gavrilina, G., Milbrandt, J. Science (1996) [Pubmed]
  25. Effects of castration and chronic steroid treatments on hypothalamic gonadotropin-releasing hormone content and pituitary gonadotropins in male wild-type and estrogen receptor-alpha knockout mice. Lindzey, J., Wetsel, W.C., Couse, J.F., Stoker, T., Cooper, R., Korach, K.S. Endocrinology (1998) [Pubmed]
  26. Genetic rescue of follicle-stimulating hormone beta-deficient mice. Kumar, T.R., Low, M.J., Matzuk, M.M. Endocrinology (1998) [Pubmed]
  27. Cloning and gene expression of a cDNA for the chicken follicle-stimulating hormone (FSH)-beta-subunit. Shen, S.T., Yu, J.Y. Gen. Comp. Endocrinol. (2002) [Pubmed]
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