The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

FSHB  -  follicle stimulating hormone, beta...

Homo sapiens

Synonyms: FSH-B, FSH-beta, Follicle-stimulating hormone beta subunit, Follitropin beta chain, Follitropin subunit beta
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of FSHB


High impact information on FSHB

  • Bone mass is increased and osteoclastic resorption is decreased in haploinsufficient FSHbeta+/- mice with normal ovarian function, suggesting that the skeletal action of FSH is estrogen independent [6].
  • Neither FSHbeta nor FSH receptor (FSHR) null mice have bone loss despite severe hypogonadism [6].
  • Our results demonstrate close physical linkage between FSHB and the WAGR locus, suggest a gene order for the four deleted markers and exclude other markers tested from this region [1].
  • Inhibin B is the major component of the testicular negative feedback signal governing FSH beta gene expression and FSH secretion, and the evidence for this view is presented [7].
  • The most common hormonal characteristic of gonadotroph cell adenomas in vivo is hypersecretion of FSH, which is often accompanied by hypersecretion of FSH beta and alpha-subunit and less often by hypersecretion of LH beta or intact LH [8].

Chemical compound and disease context of FSHB

  • CONCLUSION(S): The Cys82Arg mutation in a male with normal puberty and azoospermia results in profound deficiency of FSH in vitro, thereby confirming the molecular basis of hypogonadism in this patient and documenting the importance of the Cys residue at position 82 of the FSHbeta subunit [9].
  • Although FSH beta and LH beta mRNAs were found with similar frequencies in nonfunctioning adenomas, expression of FSH beta mRNA was generally much more abundant [10].
  • Immunocytochemistry demonstrated glycoprotein expression in somatotroph adenomas (LHbeta: 13%, FSHbeta: 26%, TSHbeta: 30%, alphaSU: 46%) more frequently than in lactotroph, corticotroph and null cell adenomas [11].
  • Patients with varicocele showed (median and range): LH B (mlU/ml): 0.40 (0.40-2.1); LH Mx.: 3.7 (1.1-15); FSH B (mlU/ml): 1.95 (0.40-4.5); FSH Mx.: 4.9 (3.1-10); T B (ng/ml): 0.2 (0.1-1.5); T Post.: 2.25 (0.82-11.5) [12].
  • Humans with FSH beta gene mutations tend to have a more severe phenotype than those with FSHR gene mutations, although infertility and varying degrees of impaired sex steroid production occur in both types of mutations [13].

Biological context of FSHB

  • At 11p13, the frequencies of LOH were 20% (9/46) at the FSHB locus, 9% (5/53) at the WT1 locus, and 15% (6/41) at the CAT locus [14].
  • A new gene (239FB) with predominant and differential expression in fetal brain has recently been isolated from a chromosome 11p13-p14 boundary area near FSHB [15].
  • The potassium channel gene HK1 maps to human chromosome 11p14.1, close to the FSHB gene [16].
  • High resolution banding cytogenetic analysis and molecular characterization using 11p13 DNA markers showed a tiny deletion encompassing the gene for CAT but sparing the gene for FSHB [17].
  • Haplotype structure of FSHB, the beta-subunit gene for fertility-associated follicle-stimulating hormone: possible influence of balancing selection [3].

Anatomical context of FSHB


Associations of FSHB with chemical compounds


Physical interactions of FSHB

  • Six LHX3-binding sites were characterized within the FSHbeta promoter, including three within a proximal region that also mediates gene regulation by other transcription factors and activin [26].
  • The unique functions of this hormone are provided by the FSH receptor-binding beta-subunit encoded by the FSHB gene [3].
  • With the exception of anti-22-39, all of the remaining antisera bound to hFSH alpha r/a. None of the antisera bound to hFSH beta [27].
  • Evidence that a calmodulin-like calcium-binding domain of the FSH beta-subunit is involved in FSH-induced calcium uptake by Sertoli cells [28].

Co-localisations of FSHB

  • In 7 cases, TSH-beta was positive, and in some cases, TSH-beta was colocalized in the same tumour cells which contained alpha-subunit and FSH-beta subunit [29].

Regulatory relationships of FSHB

  • We demonstrate that in both heterologous and pituitary gonadotrope cells, specific LHX3 isoforms activate the FSH beta-subunit promoter, but not the proximal LHbeta promoter [26].
  • Transfection of both ALK4(TD) and ALK7(TD) stimulated Smad2/3 phosphorylation, and the effects of both receptors on Fshb promoter activity were inhibited by depletion of endogenous Smad3 protein levels [30].
  • The FSH beta gene is expressed in gonadotropes where its expression is controlled primarily by activin and inhibin, with additional regulation by GnRH [31].
  • Recent studies on transcriptional regulation of the ovine FSH beta-subunit gene (oFSHbeta) have defined two functional activating protein-1 (AP-1) enhancers in the proximal promoter (located at -120 and -83 bp) that are probably physiologically important for FSHbeta expression [32].
  • Recently, we reported evidence that Prop-1 directly regulates expression of the porcine FSHbeta gene, thus providing a novel advance in understanding the function of Prop-1 in FSH/LH production and hypogonadism [33].

Other interactions of FSHB

  • In the current study we demonstrate that bLH, hCG, hCG beta, hCG alpha, and FSH alpha are recognized by the pituitary GalNAc-transferase in vitro, whereas oFSH, hFSH, and hFSH beta are not (b-, h-, and o-indicate bovine, human, and ovine) [34].
  • In summary, these results identify single important residues in the long loop (between Y33 and F53) of the hFSH beta-subunit which are required for proper subunit interactions that provide conformational stability which in turn is necessary for FSH-receptor interaction [35].
  • Mutations of the proximal binding sites demonstrate their importance for LHX3 induction of the FSHbeta promoter and basal promoter activity in gonadotrope cells [26].
  • In the WiT-13 tumor both maternal and paternal chromosomes 11 are retained; D11S87 is deleted homozygously and FSHB hemizygously [36].
  • The human BDNF gene maps between FSHB and HVBS1 at the boundary of 11p13-p14 [37].

Analytical, diagnostic and therapeutic context of FSHB

  • Next, synthetic peptides corresponding to the sequence of hFSH beta were used in an enzyme-linked immunosorbent assay to map this epitope [38].
  • Sequence analysis of the FSH beta-subunit gene indicated that she is homozygous for a two nucleotide frameshift deletion in the coding sequence [39].
  • Southern blot analyses of human genomic DNA are consistent with a single copy of the FSH beta gene per haploid genome [5].
  • Unexpectedly, these siblings with isolated FSH deficiency due to a nonsense FSH beta mutation had some evidence of puberty, suggesting that other factors might preserve gonadal steroidogenesis in the absence of FSH or that current bioassays cannot discriminate among very low FSH levels [40].
  • INTERVENTION(S): Levels of FSH, LH, LHRH provocation test, karyotyping, genomic analysis on the Y-chromosomal AZF region and sequencing of the FSHB gene, FSH treatment [41].


  1. The beta-subunit of follicle-stimulating hormone is deleted in patients with aniridia and Wilms' tumour, allowing a further definition of the WAGR locus. Glaser, T., Lewis, W.H., Bruns, G.A., Watkins, P.C., Rogler, C.E., Shows, T.B., Powers, V.E., Willard, H.F., Goguen, J.M., Simola, K.O. Nature (1986) [Pubmed]
  2. The T-ALL specific t(11;14)(p13;q11) translocation breakpoint cluster region is located near to the Wilms' tumour predisposition locus. Boehm, T., Lavenir, I., Forster, A., Wadey, R.B., Cowell, J.K., Harbott, J., Lampert, F., Waters, J., Sherrington, P., Couillin, P. Oncogene (1988) [Pubmed]
  3. Haplotype structure of FSHB, the beta-subunit gene for fertility-associated follicle-stimulating hormone: possible influence of balancing selection. Grigorova, M., Rull, K., Laan, M. Ann. Hum. Genet. (2007) [Pubmed]
  4. DNA sequence and regional assignment of the human follicle-stimulating hormone beta-subunit gene to the short arm of human chromosome 11. Watkins, P.C., Eddy, R., Beck, A.K., Vellucci, V., Leverone, B., Tanzi, R.E., Gusella, J.F., Shows, T.B. DNA (1987) [Pubmed]
  5. Human follicle-stimulating hormone beta-subunit gene encodes multiple messenger ribonucleic acids. Jameson, J.L., Becker, C.B., Lindell, C.M., Habener, J.F. Mol. Endocrinol. (1988) [Pubmed]
  6. FSH directly regulates bone mass. Sun, L., Peng, Y., Sharrow, A.C., Iqbal, J., Zhang, Z., Papachristou, D.J., Zaidi, S., Zhu, L.L., Yaroslavskiy, B.B., Zhou, H., Zallone, A., Sairam, M.R., Kumar, T.R., Bo, W., Braun, J., Cardoso-Landa, L., Schaffler, M.B., Moonga, B.S., Blair, H.C., Zaidi, M. Cell (2006) [Pubmed]
  7. The functional significance of FSH in spermatogenesis and the control of its secretion in male primates. Plant, T.M., Marshall, G.R. Endocr. Rev. (2001) [Pubmed]
  8. Gonadotroph cell adenomas of the pituitary. Snyder, P.J. Endocr. Rev. (1985) [Pubmed]
  9. Analysis of the Cys82Arg mutation in follicle-stimulating hormone beta (FSHbeta) using a novel FSH expression vector. Clark, A.D., Layman, L.C. Fertil. Steril. (2003) [Pubmed]
  10. Glycoprotein hormone genes are expressed in clinically nonfunctioning pituitary adenomas. Jameson, J.L., Klibanski, A., Black, P.M., Zervas, N.T., Lindell, C.M., Hsu, D.W., Ridgway, E.C., Habener, J.F. J. Clin. Invest. (1987) [Pubmed]
  11. Free alpha-subunit and intact TSH secretion in vitro are closely associated in human somatotroph adenomas. Aylwin, S.J., King, A., Blenke, A., Geddes, J.F., Wood, D.F., Monson, J.P., Burrin, J.M. Eur. J. Endocrinol. (1998) [Pubmed]
  12. Varicocele in prepubertal boys. Evaluation of clinical Doppler and hormonal findings. Fideleff, H.L., Boquete, H., Ruibal, G., Suärez, M., Sobrado, P., Zanchetti, F., Perco, M., Holland, M. Medicina (B Aires) (1996) [Pubmed]
  13. Mutations in the follicle-stimulating hormone-beta (FSH beta) and FSH receptor genes in mice and humans. Layman, L.C. Seminars in reproductive medicine. (2000) [Pubmed]
  14. Correlation of loss of heterozygosity at 11p with tumour progression and survival in non-small cell lung cancer. Fong, K.M., Zimmerman, P.V., Smith, P.J. Genes Chromosomes Cancer (1994) [Pubmed]
  15. cDNA sequence, genomic organization, and evolutionary conservation of a novel gene from the WAGR region. Schwartz, F., Eisenman, R., Knoll, J., Gessler, M., Bruns, G. Genomics (1995) [Pubmed]
  16. The potassium channel gene HK1 maps to human chromosome 11p14.1, close to the FSHB gene. Gessler, M., Grupe, A., Grzeschik, K.H., Pongs, O. Hum. Genet. (1992) [Pubmed]
  17. Molecular analysis of a reciprocal translocation t(5;11) (q11;p13) in a WAGR patient. Puissant, H., Azoulay, M., Serre, J.L., Piet, L.L., Junien, C. Hum. Genet. (1988) [Pubmed]
  18. Monoclonal antibodies against human follicle-stimulating hormone. Hojo, H., Ryan, R.J. Endocrinology (1985) [Pubmed]
  19. Amino acid sequence of the beta subunit of follicle-stimulating hormone from human pituitary glands. Saxena, B.B., Rathnam, P. J. Biol. Chem. (1976) [Pubmed]
  20. A synthetic peptide corresponding to human FSH beta-subunit 33-53 binds to FSH receptor, stimulates basal estradiol biosynthesis, and is a partial antagonist of FSH. Santa Coloma, T.A., Dattatreyamurty, B., Reichert, L.E. Biochemistry (1990) [Pubmed]
  21. Synthesis of multi-subunit domain gonadotropin complexes: a model for alpha/beta heterodimer formation. Ben-Menahem, D., Hyde, R., Pixley, M., Berger, P., Boime, I. Biochemistry (1999) [Pubmed]
  22. Evidence for the existence of a large molecular weight protein in human pituitary tissue having follicle stimulating hormone activity. Reichert, L.E., Ramsey, R.B. J. Clin. Endocrinol. Metab. (1977) [Pubmed]
  23. Determination of alpha-subunit contact regions of human follicle-stimulating hormone beta-subunit using synthetic peptides. Santa-Coloma, T.A., Reichert, L.E. J. Biol. Chem. (1991) [Pubmed]
  24. Identification of amino acids in the C-terminal region of human follicle-stimulating hormone (FSH) beta-subunit involved in binding to human FSH receptor. Lindau-Shepard, B., Roth, K.E., Dias, J.A. Endocrinology (1994) [Pubmed]
  25. Cysteine residues in a synthetic peptide corresponding to human follicle-stimulating hormone beta-subunit receptor-binding domain 81-95 [hFSH-beta-(81-95)] modulate the in vivo effects of hFSH-beta-(81-95) on the mouse estrous cycle. Grasso, P., Rozhavskaya-Arena, M., Reichert, L.E. Regul. Pept. (1999) [Pubmed]
  26. Regulation of the follicle-stimulating hormone beta gene by the LHX3 LIM-homeodomain transcription factor. West, B.E., Parker, G.E., Savage, J.J., Kiratipranon, P., Toomey, K.S., Beach, L.R., Colvin, S.C., Sloop, K.W., Rhodes, S.J. Endocrinology (2004) [Pubmed]
  27. Topographic analysis of the alpha-subunit of human follicle-stimulating hormone using site-specific antipeptide antisera. Weiner, R.S., Andersen, T.T., Dias, J.A. Endocrinology (1990) [Pubmed]
  28. Evidence that a calmodulin-like calcium-binding domain of the FSH beta-subunit is involved in FSH-induced calcium uptake by Sertoli cells. Grasso, P., Reichert, L.E. J. Mol. Endocrinol. (1994) [Pubmed]
  29. Immunohistochemical studies of human FSH producing pituitary adenomas. Osamura, R.Y., Watanabe, K. Virchows Archiv. A, Pathological anatomy and histopathology. (1988) [Pubmed]
  30. Activin B can signal through both ALK4 and ALK7 in gonadotrope cells. Bernard, D.J., Lee, K.B., Santos, M.M. Reprod. Biol. Endocrinol. (2006) [Pubmed]
  31. The gonadotropin genes: evolution of distinct mechanisms for hormonal control. Albanese, C., Colin, I.M., Crowley, W.F., Ito, M., Pestell, R.G., Weiss, J., Jameson, J.L. Recent Prog. Horm. Res. (1996) [Pubmed]
  32. Transcriptional activation of the ovine follicle-stimulating hormone beta-subunit gene by gonadotropin-releasing hormone: involvement of two activating protein-1-binding sites and protein kinase C. Strahl, B.D., Huang, H.J., Sebastian, J., Ghosh, B.R., Miller, W.L. Endocrinology (1998) [Pubmed]
  33. High level expression of Prop-1 gene in gonadotropic cell lines. Aikawa, S., Sato, T., Ono, T., Kato, T., Kato, Y. J. Reprod. Dev. (2006) [Pubmed]
  34. Recognition by the glycoprotein hormone-specific N-acetylgalactosaminetransferase is independent of hormone native conformation. Smith, P.L., Baenziger, J.U. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  35. Follitropin conformational stability mediated by loop 2 beta effects follitropin-receptor interaction. Roth, K.E., Dias, J.A. Biochemistry (1996) [Pubmed]
  36. Homozygous deletion of a DNA marker from chromosome 11p13 in sporadic Wilms tumor. Lewis, W.H., Yeger, H., Bonetta, L., Chan, H.S., Kang, J., Junien, C., Cowell, J., Jones, C., Dafoe, L.A. Genomics (1988) [Pubmed]
  37. The human BDNF gene maps between FSHB and HVBS1 at the boundary of 11p13-p14. Hanson, I.M., Seawright, A., van Heyningen, V. Genomics (1992) [Pubmed]
  38. Mapping of an assembled epitope of human follicle-stimulating hormone-beta utilizing monoclonal antibodies, synthetic peptides, and hormone-receptor inhibition. Vakharia, D.D., Dias, J.A., Thakur, A.N., Andersen, T.T., O'Shea, A. Endocrinology (1990) [Pubmed]
  39. Primary amenorrhoea and infertility due to a mutation in the beta-subunit of follicle-stimulating hormone. Matthews, C.H., Borgato, S., Beck-Peccoz, P., Adams, M., Tone, Y., Gambino, G., Casagrande, S., Tedeschini, G., Benedetti, A., Chatterjee, V.K. Nat. Genet. (1993) [Pubmed]
  40. FSH beta gene mutations in a female with partial breast development and a male sibling with normal puberty and azoospermia. Layman, L.C., Porto, A.L., Xie, J., da Motta, L.A., da Motta, L.D., Weiser, W., Sluss, P.M. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  41. Apparent primary follicle-stimulating hormone deficiency is a rare cause of treatable male infertility. Giltay, J.C., Deege, M., Blankenstein, R.A., Kastrop, P.M., Wijmenga, C., Lock, T.T. Fertil. Steril. (2004) [Pubmed]
WikiGenes - Universities