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Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility

Abstract

Follicle stimulating hormone (FSH) is a member of the glycoprotein hormone family that includes luteinizing hormone (LH), thyroid stimulating hormone, and chorionic gonadotropin. These heterodimeric hormones share a common α subunit and differ in their hormone-specific β subunit. The biological activity is conferred only by the heterodimers. FSH and LH are synthesized in the same cells of the pituitary, the gonadotrophs1,2. FSH receptors are localized to Sertoli cells of the testes and granulosa cells of the ovary1,2. Minimal data has been accumulated so far involving human mutations in the FSHβ, LHβ, or the gonadotropin receptor genes. There are no known mouse strains with mutations in the FSHβ gene. To generate animal models for human diseases involving the gonadotropin signal transduction pathway, we produced mice deficient in the FSHβ subunit and therefore in FSH using ES cell technology. FSH-deficient females are infertile due to a block in folliculogenesis prior to antral follicle formation. Although FSH was predicted to be necessary for spermatogenesis and Sertoli cell growth in males, FSH-deficient males are fertile despite having small testes. Our findings have important implications for male contraceptive development in humans.

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References

  1. Pierce, J.G. & Parsons, T.F. Glycoprotein hormones: structure and function. Annu. Rev. Biochem. 50, 465–495 (1981).

    Article  CAS  Google Scholar 

  2. Bousfield, G.R., Perry, W.M. & Ward, D.N. Gonadotropins: chemistry and biosynthesis. In The Physiology of Reproduction (eds Knobil, E. & Neill, J.D.) 1749–1792 (Raven Press, New York, 1994).

    Google Scholar 

  3. Camper, S.A. et al. Implementing transgenic and embryonic stem cell technology to study gene expression, cell–cell interactions and gene function. Biol. Reprod. 52, 246–257 (1995).

    Article  CAS  Google Scholar 

  4. Nishimori, K. & Matzuk, M.M. Transgenic mice in the analysis of reproductive development and function. Rev. Reprod. 1, 203–212 (1996).

    Article  CAS  Google Scholar 

  5. Kendall, S.K., Samuelson, L.C., Saunders, T.L., Wood, R.I. & Camper, S.A. Targeted disruption of the pituitary glycoprotein hormone alpha-subunit produces hypogonadal and hypothyroid mice. Genes Develop. 9, 2007–2019 (1995).

    Article  CAS  Google Scholar 

  6. Matzuk, M.M., Kumar, T.R. & Bradley, A. Different phenotypes for mice deficient in either activins or activin receptor type II. Nature 374, 356–360 (1995).

    Article  CAS  Google Scholar 

  7. Kluin, P.M., Kramer, M.F. & DeRooij, D.G. Proliferation of spermatogonia and Sertoli cells in maturing mice. Anat. Embryol. 169, 73–78 (1984).

    Article  CAS  Google Scholar 

  8. Orth, J.M. The role of follicle-stimulating hormone in controlling Sertoli cell proliferation in testes of fetal rats. Endocrinology 115, 1248–1255 (1984).

    Article  CAS  Google Scholar 

  9. Matthews, C.H. et al. Primary amenorrhea and infertility due to a mutation in the β-subunit of follicle-stimulating hormone. Nature Genet. 5, 83–86 (1993).

    Article  CAS  Google Scholar 

  10. Aittomáki, K. et al. Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell 82, 959–968 (1995).

    Article  Google Scholar 

  11. Aittomã, K. et al. Clinical features of primary ovarian failure caused by a point mutation in the follicle-stimulating hormone receptor gene. J. Clin. Endocr. Metab. 81, 3722–3726 (1996).

    Google Scholar 

  12. Tapanainen, J.S., Aittomãki, K., Min, J., Vaskivmo, T. & Huhtaniemi, I. Men homozygous for an inactivating mutation of the follicle-stimulating hormone (FSH) receptor gene present variable suppression of spermatogenesis and fertility. Nature Genet. 15, 205–206 (1997).

    Article  CAS  Google Scholar 

  13. Aldhous, P. A booster for contraceptive vaccines. Science 266, 1484–1486 (1994).

    Article  CAS  Google Scholar 

  14. Matzuk, M.M., Finegold, M.J., Su, J-G.J., Hsueh, A.J.W. & Bradley, A. α-lnhibin is a tumour-suppressor gene with gonadal specificity in mice. Nature 360, 313–319 (1992).

    Article  CAS  Google Scholar 

  15. Kumar, T.R., Kelly, M., Mortrud, M., Low, M.J. & Matzuk, M.M. Cloning of the mouse gonadotropin β subunit genes. I. Structure of the follicle stimulating hormone β subunit gene. Gene 166, 333–334 (1995).

    Article  CAS  Google Scholar 

  16. Dong, J. et al. Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 381, 531–535 (1996).

    Article  Google Scholar 

  17. Laboratory manual for the examination of human semen and semen-cervical mucus interaction. (Cambridge University Press, Cambridge, 1992).

  18. Hogan, B., Beddington, R., Costantini, F. & Lucy, E. in Manipulating the Mouse Embryo.A Laboratory Manual 2nd ed. (Cold Spring Harbor Laboratory Press, New York, 1994).

  19. Kumar, T.R., Fairchild-Huntress, V. & Low, M.J. Gonadotrope-specific expression of the human follicle-stimulating hormone β-subunit gene in pituitaries of transgenic mice. Molec. Endocrinol. 6, 81–90 (1992).

    CAS  Google Scholar 

  20. Harlow, E. & Lane, D., In Antibodies. A Laboratory Manual 2nd ed. (Cold Spring Harbor Laboratory Press, New York, 1988).

  21. Kumar, T.R. & Low, M.J. Hormonal regulation of human follicle-stimulating hormone-β subunit gene expression: GnRH stimulation and GnRH-independent androgen inhibition. Neuroendocrinolog 61, 628–637 (1995).

    Article  CAS  Google Scholar 

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Correspondence to Martin M. Matzuk.

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Kumar, T., Wang, Y., Lu, N. et al. Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat Genet 15, 201–204 (1997). https://doi.org/10.1038/ng0297-201

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