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FSHβ knockout mouse model: a decade ago and into the future

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Abstract

In 1997, more than 10 years ago now, we first reported the phenotypes of follicle stimulating hormone (FSH) β null mice. Since then, these mice have been useful for various physiological and genetic studies in reproductive biology. More recently, extra-gonadal functions of FSH have been discovered in bone. These studies opened up exciting avenues of new research on osteoporosis in postmenopausal women. Several genomics and proteomics tools and novel strategies to spatio-temporally restricting gene expression in vivo are available now. It is hoped that with the aid of these and other emerging technologies, an integrated network of FSH signaling pathways in various tissues would emerge in the near future. Undoubtedly, the coming 10 years should be more exciting to explore this “fertile” area of reproductive physiology research.

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References

  1. T.R. Kumar, What have we learned about gonadotropin function from gonadotropin subunit and receptor knockout mice? Reproduction 130, 293–302 (2005)

    Article  CAS  PubMed  Google Scholar 

  2. T.R. Kumar, Gonadotropin gene targeting and biological implications. Endocrine 26, 227–233 (2005)

    Article  CAS  PubMed  Google Scholar 

  3. T.R. Kumar, Mouse models for gonadotropins: a 15-year Saga. Mol. Cell. Endocrinol. 260–262, 249–254 (2007)

    Article  PubMed  Google Scholar 

  4. N.R. Moudgal, M.R. Sairam, Is there a true requirement for follicle stimulating hormone in promoting spermatogenesis and fertility in primates? Hum. Reprod. 13, 916–919 (1998)

    Article  CAS  PubMed  Google Scholar 

  5. B.E. Greer, J.S. Berek, Gynecologic oncology: treatment rationale and technique (Elsevier Publishing, New York, 1991)

    Google Scholar 

  6. T.R. Kumar, L.A. Donehower, A. Bradley, M.M. Matzuk, Transgenic mouse models for tumour-suppressor genes. J. Intern. Med. 238, 233–238 (1995)

    Article  CAS  PubMed  Google Scholar 

  7. M.M. Matzuk, M.J. Finegold, J.G. Su, A.J. Hsueh, A. Bradley, Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice. Nature 360, 313–319 (1992)

    Article  CAS  PubMed  Google Scholar 

  8. T.R. Kumar, Y. Wang, N. Lu, M.M. Matzuk, Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat. Genet. 15, 201–204 (1997)

    Article  CAS  PubMed  Google Scholar 

  9. T.R. Kumar, M.J. Low, Gonadal steroid hormone regulation of human and mouse follicle stimulating hormone beta-subunit gene expression in vivo. Mol. Endocrinol. 7, 898–906 (1993)

    Article  CAS  PubMed  Google Scholar 

  10. S.D. Gharib, A. Roy, M.E. Wierman, W.W. Chin, Isolation and characterization of the gene encoding the beta-subunit of rat follicle-stimulating hormone. DNA 8, 339–349 (1989)

    CAS  PubMed  Google Scholar 

  11. J.L. Jameson, C.B. Becker, C.M. Lindell, J.F. Habener, Human follicle-stimulating hormone beta-subunit gene encodes multiple messenger ribonucleic acids. Mol. Endocrinol. 2, 806–815 (1988)

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  14. G. Meduri, A. Bachelot, M.P. Cocca, C. Vasseur, P. Rodien, F. Kuttenn, P. Touraine, M. Misrahi, Molecular pathology of the FSH receptor: new insights into FSH physiology. Mol. Cell. Endocrinol. 282, 130–142 (2008)

    Article  CAS  PubMed  Google Scholar 

  15. A.M. Matsumoto, A.E. Karpas, W.J. Bremner, Chronic human chorionic gonadotropin administration in normal men: evidence that follicle-stimulating hormone is necessary for the maintenance of quantitatively normal spermatogenesis in man. J. Clin. Endocrinol. Metab. 62, 1184–1192 (1986)

    Article  CAS  PubMed  Google Scholar 

  16. N.R. Moudgal, M.R. Sairam, H.N. Krishnamurthy, S. Sridhar, H. Krishnamurthy, H. Khan, Immunization of male bonnet monkeys (M. radiata) with a recombinant FSH receptor preparation affects testicular function and fertility. Endocrinology 38, 3065–3068 (1997)

    Article  Google Scholar 

  17. J. Singh, D.J. Handelsman, Neonatal administration of FSH increases Sertoli cell numbers and spermatogenesis in gonadotropin-deficient (hpg) mice. J. Endocrinol. 151, 37–48 (1996)

    Article  CAS  PubMed  Google Scholar 

  18. M. Gossen, H. Bujard, Studying gene function in eukaryotes by conditional gene inactivation. Annu. Rev. Genet. 36, 153–173 (2002)

    Article  CAS  PubMed  Google Scholar 

  19. S. Lamartina, G. Roscilli, C.D. Rinaudo, E. Sporeno, L. Silvi, W. Hillen, H. Bujard, R. Cortese, G. Ciliberto, C. Toniatti, Stringent control of gene expression in vivo by using novel doxycycline-dependent trans-activators. Hum. Gene Ther. 13, 199–210 (2002)

    Article  CAS  PubMed  Google Scholar 

  20. K. Schonig, F. Schwenk, K. Rajewsky, H. Bujard, Stringent doxycycline dependent control of CRE recombinase in vivo. Nucleic Acids Res. 30, e134 (2002)

    Article  PubMed  Google Scholar 

  21. E. Vigna, S. Cavalieri, L. Ailles, M. Geuna, R. Loew, H. Bujard, L. Naldini, Robust and efficient regulation of transgene expression in vivo by improved tetracycline-dependent lentiviral vectors. Mol. Ther. 5, 252–261 (2002)

    Article  CAS  PubMed  Google Scholar 

  22. P.J. Baker, P. Pakarinen, I.T. Huhtaniemi, M.H. Abel, H.M. Charlton, T.R. Kumar, P.J. O’Shaughnessy, Failure of normal Leydig cell development in follicle-stimulating hormone (FSH) receptor-deficient mice, but not FSHbeta-deficient mice: role for constitutive FSH receptor activity. Endocrinology 144, 138–145 (2003)

    Article  CAS  PubMed  Google Scholar 

  23. T.R. Kumar, G. Palapattu, P. Wang, T.K. Woodruff, I. Boime, M.C. Byrne, M.M. Matzuk, Transgenic models to study gonadotropin function: the role of follicle-stimulating hormone in gonadal growth and tumorigenesis. Mol. Endocrinol. 13, 851–865 (1999)

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  25. T.R. Kumar, M.J. Low, M.M. Matzuk, Genetic rescue of follicle-stimulating hormone beta-deficient mice. Endocrinology 139, 3289–3295 (1998)

    Article  CAS  PubMed  Google Scholar 

  26. V. Garcia-Campayo, I. Boime, X. Ma, D. Daphna-Iken, T.R. Kumar, A single-chain tetradomain glycoprotein hormone analog elicits multiple hormone activities in vivo. Biol. Reprod. 72, 301–308 (2005)

    Article  CAS  PubMed  Google Scholar 

  27. A. Jablonka-Shariff, T.R. Kumar, J. Eklund, A. Comstock, I. Boime, Single-chain, triple-domain gonadotropin analogs with disulfide bond mutations in the alpha-subunit elicit dual follitropin and lutropin activities in vivo. Mol. Endocrinol. 20, 1437–1446 (2006)

    Article  CAS  PubMed  Google Scholar 

  28. N.G. Wreford, T. Rajendra Kumar, M.M. Matzuk, D.M. de Kretser, Analysis of the testicular phenotype of the follicle-stimulating hormone beta-subunit knockout and the activin type II receptor knockout mice by stereological analysis. Endocrinology 142, 2916–2920 (2001)

    Article  CAS  PubMed  Google Scholar 

  29. H. Johnston, P.J. Baker, M. Abel, H.M. Charlton, G. Jackson, L. Fleming, T.R. Kumar, P.J. O’Shaughnessy, Regulation of Sertoli cell number and activity by follicle-stimulating hormone and androgen during postnatal development in the mouse. Endocrinology 145, 318–329 (2004)

    Article  CAS  PubMed  Google Scholar 

  30. C. Lukas-Croisier, C. Lasala, J. Nicaud, P. Bedecarras, T.R. Kumar, M. Dutertre, M.M. Matzuk, J.Y. Picard, N. Josso, R. Rey, Follicle-stimulating hormone increases testicular anti-Mullerian hormone (AMH) production through sertoli cell proliferation and a nonclassical cyclic adenosine 5′-monophosphate-mediated activation of the AMH Gene. Mol. Endocrinol. 17, 550–561 (2003)

    Article  CAS  PubMed  Google Scholar 

  31. G. Shetty, C.C. Weng, K.L. Porter, Z. Zhang, P. Pakarinen, T.R. Kumar, M.L. Meistrich, Spermatogonial differentiation in juvenile spermatogonial depletion (jsd) mice with androgen receptor or follicle-stimulating hormone mutations. Endocrinology 147, 3563–3570 (2006)

    Article  CAS  PubMed  Google Scholar 

  32. A.L. Durlinger, M.J. Gruijters, P. Kramer, B. Karels, T.R. Kumar, M.M. Matzuk, U.M. Rose, F.H. de Jong, J.T. Uilenbroek, J.A. Grootegoed, A.P. Themmen, Anti-Mullerian hormone attenuates the effects of FSH on follicle development in the mouse ovary. Endocrinology 142, 4891–4899 (2001)

    Article  CAS  PubMed  Google Scholar 

  33. J. Zhou, T.R. Kumar, M.M. Matzuk, C. Bondy, Insulin-like growth factor I regulates gonadotropin responsiveness in the murine ovary. Mol. Endocrinol. 11, 1924–1933 (1997)

    Article  CAS  PubMed  Google Scholar 

  34. C.M. Combelles, M.J. Carabatsos, T.R. Kumar, M.M. Matzuk, D.F. Albertini, Hormonal control of somatic cell oocyte interactions during ovarian follicle development. Mol. Reprod. Dev. 69, 347–355 (2004)

    Article  CAS  PubMed  Google Scholar 

  35. L. Sun, Y. Peng, A.C. Sharrow, J. Iqbal, Z. Zhang, D.J. Papachristou, S. Zaidi, L.L. Zhu, B.B. Yaroslavskiy, H. Zhou, A. Zallone, M.R. Sairam, T.R. Kumar, W. Bo, J. Braun, L. Cardoso-Landa, M.B. Schaffler, B.S. Moonga, H.C. Blair, M. Zaidi, FSH directly regulates bone mass. Cell 125, 247–260 (2006)

    Article  CAS  PubMed  Google Scholar 

  36. M.J. Seibel, C.R. Dunstan, H. Zhou, C.M. Allan, D.J. Handelsman, Sex steroids, not FSH, influence bone mass. Cell 127, 1079 (2006). author reply 1080–1071

    Article  CAS  PubMed  Google Scholar 

  37. N. Danilovich, M.R. Sairam, Targeting gonadotropin receptor genes: reproductive biology, aging, and related health implications. Endocrine 26, 219–226 (2005)

    Article  CAS  PubMed  Google Scholar 

  38. A. Dierich, M.R. Sairam, L. Monaco, G.M. Fimia, A. Gansmuller, M. LeMeur, P. Sassone-Corsi, Impairing follicle-stimulating hormone (FSH) signaling in vivo: targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance. Proc. Natl Acad. Sci. USA 95, 13612–13617 (1998)

    Article  CAS  PubMed  Google Scholar 

  39. M.H. Abel, I. Huhtaniemi, P. Pakarinen, T.R. Kumar, H.M. Charlton, Age-related uterine and ovarian hypertrophy in FSH receptor knockout and FSHbeta subunit knockout mice. Reproduction 125, 165–173 (2003)

    Article  CAS  PubMed  Google Scholar 

  40. C.V. Rao, An overview of the past, present, and future of nongonadal LH/hCG actions in reproductive biology and medicine. Semin. Reprod. Med. 19, 7–17 (2001)

    Article  CAS  PubMed  Google Scholar 

  41. C.V. Rao, Z.M. Lei, The past, present and future of nongonadal LH/hCG actions in reproductive biology and medicine. Mol. Cell. Endocrinol. 269, 2–8 (2007)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

I am fortunate to have worked under the tutelage of Professor K. Muralidhar, University of Delhi, India, who introduced me to gonadotropin research. I thank Professor Malcolm Low, Vollum Institute, Portland, for providing me an opportunity to work on FSHβ transgenic mice, clone mouse FSHβ gene in his laboratory and allowing me to continue the FSH project. I am grateful to Professor Marty Matzuk, Baylor College of Medicine, Houston, who lent his support and encouragement throughout the course of generating and characterizing FSHβ null and various other transgenic lines of mice. I also thank all my USA and foreign collaborators, particularly, Mone Zaidi, Mount Sinai School of Medicine, for convincing me that FSH could have extra-gonadal actions and for many thought-provoking telephone discussions on estrogen and FSH actions on bone biology. My thanks are also due to Dr. Huizhen Wang, Mr. Phillip Stevenson my colleagues at the University of Kansas Medical Center, for their dedication to the studies in my laboratory with FSHβ null mice that received support from the NIH (HD043945; RR024214), and The Hall Family Foundation, Kansas City, MO.

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  1. Departments of Molecular & Integrative Physiology and Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, 66160, USA

    T. Rajendra Kumar

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Kumar, T.R. FSHβ knockout mouse model: a decade ago and into the future. Endocr 36, 1–5 (2009). https://doi.org/10.1007/s12020-009-9199-6

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