Skip to main content
SpringerLink
Log in

Gonadotropin gene targeting and biological implications

  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Pituitary gonadotropins FSH and LH are heterodimeric glycoproteins consisting of a common alpha and a hormone-specific beta subunit that are non-covalently linked. These hormones orchestrate gonadal growth, differentiation, and function by regulating both steroidogenesis and gametogenesis. Advances in the past two decades in manipulating the mouse genome by site-specific mutagenesis have heralded a new dimension to our understanding of the biology of gonadotropins. Using these gene-targeting approaches, knockout mice lacking the hormone-specific gonadotropin subunits, and hence the functional dimeric hormones, have been generated. These individual gonadotropin-deficient mice are useful to delineate the distinct in vivo biological roles of FSH and LH. These mice also serve as valuable genetic tools to study the signaling mechanisms within the gonads and help a better understanding of some forms of human infertility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Pierce, J. G. and Parsons, T. F. (1981). Annu. Rev. Biochem. 50, 465–495.

    Article  PubMed  CAS  Google Scholar 

  2. Bousfield, G. R., Perry, W. M., and Ward, D. N. (1994). In: The physiology of reproduction. Knobil, E. and Neill, J. D. (eds.). Raven Press: New York, pp. 1749–1792.

    Google Scholar 

  3. Ruf, F., Fink, M. Y., and Sealfon, S. C. (2003). Front. Neuroendocrinol. 24, 181–199.

    Article  PubMed  CAS  Google Scholar 

  4. Shimasaki, S., Moore, R. K., Otsuka, F., and Erickson, G. F. (2004). Endocr. Rev. 25, 72–101.

    Article  PubMed  CAS  Google Scholar 

  5. Bradley, A., Ramirez-Solis, R., Zheng, H., Hasty, P., and Davis, A. (1992). Ciba Found Symp. 165, 256–269; discussion 269–276.

    PubMed  CAS  Google Scholar 

  6. Bradley, A., Hasty, P., Davis, A., and Ramirez-Solis, R. (1992). Biotechnology (NY) 10, 534–539.

    Article  CAS  Google Scholar 

  7. Bradley, A. (1993). Recent Prog. Horm. Res. 48, 237–251.

    PubMed  CAS  Google Scholar 

  8. Ramirez-Solis, R. and Bradley, A. (1994). Curr. Opin. Biotechnol. 5, 528–533.

    Article  PubMed  CAS  Google Scholar 

  9. Justice, M. J., Zheng, B., Woychik, R. P., and Bradley, A. (1997). Methods 13, 423–436.

    Article  PubMed  CAS  Google Scholar 

  10. Bradley, A., Zheng, B., and Liu, P. (1998). Int. J. Dev. Biol. 42, 943–950.

    PubMed  CAS  Google Scholar 

  11. Mills, A. A. and Bradley, A. (2001). Trends Genet. 17, 331–339.

    Article  PubMed  CAS  Google Scholar 

  12. Yu, Y. and Bradley, A. (2001). Nat. Rev. Genet. 2, 780–790.

    Article  PubMed  CAS  Google Scholar 

  13. van der Weyden, L., Adams, D. J., and Bradley, A. (2002). Physiol. Genomics 11, 133–164.

    PubMed  Google Scholar 

  14. Capecchi, M. R. (1989). Science 244, 1288–1292.

    Article  PubMed  CAS  Google Scholar 

  15. Capecchi, M. R. (1989). Trends Genet. 5, 70–76.

    Article  PubMed  CAS  Google Scholar 

  16. Kendall, S. K., Samuelson, L. C., Saunders, T. L., Wood, R. I., and Camper, S. A. (1995). Genes Dev. 9, 2007–2019.

    PubMed  CAS  Google Scholar 

  17. Mason, A. J., Hayflick, J. S., Zoeller, R. T., et al. (1986). Science 234, 1366–1371.

    Article  PubMed  CAS  Google Scholar 

  18. Mason, A. J., Pitts, S. L., Nikolics, K., et al. (1986). Science 234, 1372–1378.

    Article  PubMed  CAS  Google Scholar 

  19. Mason, A. J., Pitts, S. L., Nikolics, K., et al. (1987). Ann. NY Acad. Sci. 513, 16–26.

    Article  PubMed  CAS  Google Scholar 

  20. Kumar, T. R., Wang, Y., Lu, N., and Matzuk, M. M. (1997). Nat. Genet. 15, 201–204.

    Article  PubMed  CAS  Google Scholar 

  21. Wreford, N. G., Kumar, T. R., Matzuk, M. M., and de Kretser, D. M. (2001). Endocrinology 142, 2916–2920.

    Article  PubMed  CAS  Google Scholar 

  22. Kumar, T. R., Varani, S., Wreford, N. G., Telfer, N. M., de Kretser, D. M., and Matzuk, M. M. (2001). Endocrinology 142, 3512–3518.

    Article  PubMed  CAS  Google Scholar 

  23. Baker, P. J., Pakarinen, P., Huhtaniemi, I. T., et al. (2003). Endocrinology 144, 138–145.

    Article  PubMed  CAS  Google Scholar 

  24. McLachlan, R. I., O’Donnell, L., Meachem, S. J., et al. (2002). Recent Prog. Horm. Res. 57, 149–179.

    Article  PubMed  CAS  Google Scholar 

  25. McLachlan, R. I., O’Donnell, L., Meachem, S. J., et al. (2002). J. Androl. 23, 149–162.

    PubMed  CAS  Google Scholar 

  26. Moudgal, N. R., Jeyakumar, M., Krishnamurthy, H. N., Sridhar, S., Krishnamurthy, H., and Martin, F. (1997). Hum. Reprod. Update 3, 335–346.

    Article  PubMed  CAS  Google Scholar 

  27. Moudgal, N. R. and Sairam, M. R. (1998). Hum. Reprod. 13, 916–919.

    Article  PubMed  CAS  Google Scholar 

  28. Plant, T. M. and Marshall, G. R. (2001). Endocr. Rev. 22, 764–786.

    Article  PubMed  CAS  Google Scholar 

  29. Furth, P. A., St Onge, L., Boger, H., et al. (1994). Proc. Natl. Acad. Sci. USA 91, 9302–9306.

    Article  PubMed  CAS  Google Scholar 

  30. Gossen, M. and Bujard, H. (2002). Annu. Rev. Genet. 36, 153–173.

    Article  PubMed  CAS  Google Scholar 

  31. Schonig, K., Schwenk, F., Rajewsky, K., and Bujard, H. (2002). Nucleic Acids Res. 30, e134.

    Google Scholar 

  32. Burns, K. H., Yan, C., Kumar, T. R., and Matzuk, M. M. (2001). Endocrinology 142, 2742–2751.

    Article  PubMed  CAS  Google Scholar 

  33. Combelles, C. M., Carabatsos, M. J., Kumar, T. R., Matzuk, M. M., and Albertini, D. F. (2004). Mol. Reprod. Dev. 69, 347–355.

    Article  PubMed  CAS  Google Scholar 

  34. Abel, M. H., Huhtaniemi, I., Pakarinen, P., Kumar, T. R., and Charlton, H. M. (2003). Reproduction 125, 165–173.

    Article  PubMed  CAS  Google Scholar 

  35. Kumar, T. R., Low, M. J., and Matzuk, M. M. (1998). Endocrinology 139, 3289–3295.

    Article  PubMed  CAS  Google Scholar 

  36. Matzuk, M. M., Finegold, M. J., Su, J. G., Hsueh, A. J., and Bradley, A. (1992). Nature 360, 313–319.

    Article  PubMed  CAS  Google Scholar 

  37. Matzuk, M. M., Finegold, M. J., Mather, J. P., Krummen, L., Lu, H., and Bradley, A. (1994). Proc. Natl. Acad. Sci. USA 91, 8817–8821.

    Article  PubMed  CAS  Google Scholar 

  38. Kumar, T. R., Wang, Y., and Matzuk, M. M. (1996). Endocrinology 137, 4210–4216.

    Article  PubMed  CAS  Google Scholar 

  39. Kumar, T. R., Palapattu, G., Wang, P., et al. (1999). Mol. Endocrinol. 13, 851–865.

    Article  PubMed  CAS  Google Scholar 

  40. Bilezikjian, L. M., Blount, A. L., Corrigan, A. Z., Leal, A., Chen, Y., and Vale, W. W. (2001). Clin. Exp. Pharmacol. Physiol. 28, 244–248.

    Article  PubMed  CAS  Google Scholar 

  41. Woodruff, T. K. (1998). Biochem. Pharmacol. 55, 953–963.

    Article  PubMed  CAS  Google Scholar 

  42. Pangas, S. A. and Woodruff, T. K. (2000). Trends Endocrinol. Metab. 11, 309–314.

    Article  PubMed  CAS  Google Scholar 

  43. Gaddy-Kurten, D., Tsuchida, K., and Vale, W. (1995). Recent Prog. Horm. Res. 50, 109–129.

    PubMed  CAS  Google Scholar 

  44. Roberts, V. J., Peto, C. A., Vale, W., and Sawchenko, P. E. (1992). Neuroendocrinology 56, 214–224.

    PubMed  CAS  Google Scholar 

  45. Cameron, V. A., Nishimura, E., Mathews, L. S., Lewis, K. A., Sawchenko, P. E., and Vale, W. W. (1994). Endocrinology 134, 799–808.

    Article  PubMed  CAS  Google Scholar 

  46. Matzuk, M. M., Kumar, T. R., and Bradley, A. (1995). Nature 374, 356–360.

    Article  PubMed  CAS  Google Scholar 

  47. Kumar, T. R., Agno, J., Janovick, J. A., Conn, P. M., and Matzuk, M. M. (2003). Mol. Cell. Endocrinol. 212, 19–27.

    Article  PubMed  CAS  Google Scholar 

  48. Coerver, K. A., Woodruff, T. K., Finegold, M. J., Mather, J., Bradley, A., and Matzuk, M. M. (1996). Mol. Endocrinol. 10, 534–543.

    Article  PubMed  CAS  Google Scholar 

  49. Josso, N. and Rey, R. (1996). Curr. Opin. Pediatr. 8, 396–400.

    Article  PubMed  CAS  Google Scholar 

  50. Josso, N. and di Clemente, N. (1997). Curr. Opin. Genet. Dev. 7, 371–377.

    Article  PubMed  CAS  Google Scholar 

  51. Josso, N., Racine, C., di Clemente, N., Rey, R., and Xavier, F. (1998). Mol. Cell. Endocrinol. 145, 3–7.

    Article  PubMed  Google Scholar 

  52. Josso, N., di Clemente, N., and Gouedard, L. (2001). Mol. Cell. Endocrinol. 179, 25–32.

    Article  PubMed  CAS  Google Scholar 

  53. Josso, N. and di Clemente, N. (2003). Trends Endocrinol. Metab. 14, 91–97.

    Article  PubMed  CAS  Google Scholar 

  54. Durlinger, A. L., Gruijters, M. J., Kramer, P., et al. (2001). Endocrinology 142, 4891–4899.

    Article  PubMed  CAS  Google Scholar 

  55. Ma, X., Dong, Y. L., Matzuk, M. M., Yashwanth, R., and Kumar, T. R. (2004). Proc. Natl. Acad. Sci. USA 101, 17294–17299.

    Article  PubMed  CAS  Google Scholar 

  56. Lei, Z. M., Mishra, S., Zou, W., et al. (2001). Mol. Endocrinol. 15, 184–200.

    Article  PubMed  CAS  Google Scholar 

  57. Zhang, F. P., Poutanen, M., Wilbertz, J., and Huhtaniemi, I. (2001). Mol. Endocrinol. 15, 172–183.

    Article  PubMed  CAS  Google Scholar 

  58. Chang, C., Chen, Y. T., Yeh, S. D., et al. (2004). Proc. Natl. Acad. Sci. USA 101, 6876–6881.

    Article  PubMed  CAS  Google Scholar 

  59. De Gendt, K., Swinnen, J. V., Saunders, P. T., et al. (2004). Proc. Natl. Acad. Sci. USA 101, 1327–1332.

    Article  PubMed  CAS  Google Scholar 

  60. Holdcraft, R. W. and Braun, R. E. (2004). Development 131, 459–467.

    Article  PubMed  CAS  Google Scholar 

  61. Markkula, M. and Huhtaniemi, I. (1996). Rev. Reprod. 1, 97–106.

    Article  PubMed  CAS  Google Scholar 

  62. Kumar, T. R. and Matzuk, M. M. (2000). In: Gene engineering and molecular models in endocrinology. Shupnik, M. A. (ed.). The Humana Press: Totowa, NJ, 2000.

    Google Scholar 

  63. Huhtaniemi, I. (2000). J. Reprod. Fertil. 119, 173–186.

    Article  PubMed  CAS  Google Scholar 

  64. Aittomaki, K., Lucena, J. L., Pakarinen, P., et al. (1995). Cell 82, 959–968.

    Article  PubMed  CAS  Google Scholar 

  65. Aittomaki, K., Herva, R., Stenman, U. H., et al. (1996). J. Clin. Endocrinol. Metab. 81, 3722–3726.

    Article  PubMed  CAS  Google Scholar 

  66. Tapanainen, J. S., Aittomaki, K., Min, J., Vaskivuo, T., and Huhtaniemi, I. T. (1997). Nat. Genet. 15, 205–206.

    Article  PubMed  CAS  Google Scholar 

  67. Matthews, C. H., Borgato, S., Beck-Peccoz, P., et al. (1993). Nat. Genet. 5, 83–86.

    Article  PubMed  CAS  Google Scholar 

  68. Huhtaniemi, I. T. (2002). Best Pract. Res. Clin. Endocrinol. Metab. 16, 123–138.

    Article  PubMed  CAS  Google Scholar 

  69. Huhtaniemi, I., Jiang, M., Nilsson, C., and Pettersson, K. (1999). Mol. Cell. Endocrinol. 151, 89–94.

    Article  PubMed  CAS  Google Scholar 

  70. Weiss, J., Axelrod, L., Whitcomb, R. W., Harris, P. E., Crowley, W. F., and Jameson, J. L. (1992). N. Engl. J. Med. 326, 179–183.

    Article  PubMed  CAS  Google Scholar 

  71. Kumar, T. R. (2001). In: Transgenics in endocrinology. Matzuk, M. M., Brown, C. E., and Kumar, T. R. (ed.). Humana Press: Totowa, pp. 425–466.

    Google Scholar 

  72. Mellon, P. L., Windle, J. J., and Weiner, R. I. (1991). Recent Prog. Horm. Res. 47, 69–93; discussion 93–66.

    PubMed  CAS  Google Scholar 

  73. Garcia-Campayo, V., Kumar, T. R., and Boime, I. (2002). Endocrinology 143, 3773–3778.

    Article  PubMed  CAS  Google Scholar 

  74. Garcia-Campayo, V., Boime, I., Ma, X., Daphna-Iken, D., and Kumar, T. R. (2005). Biol. Reprod. 72, 301–308.

    Article  PubMed  CAS  Google Scholar 

  75. Narayan, P., Meehan, T. P., and Puett, D. (2003). Biol. Reprod. 68(Suppl. 1), 312–313.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 66160, Kansas City, KS

    T. Rajendra Kumar

  2. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd., 66160, Kansas City, KS

    T. Rajendra Kumar

Authors
  1. T. Rajendra Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. Rajendra Kumar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kumar, T.R. Gonadotropin gene targeting and biological implications. Endocr 26, 227–233 (2005). https://doi.org/10.1385/ENDO:26:3:227

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/ENDO:26:3:227

Key Words

Search

Navigation