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Targeting gonadotropin receptor genes

Reproductive biology, aging, and related health implications

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Abstract

This review highlights observations gleaned from recent reports on the deletion of FSH and LH receptors in mice. Gonadal differentiation does not depend on the presence of gonadotropin receptors but development is affected to varying degrees in both sexes. In both knockouts the null females are infertile with severely underdeveloped gonads and accessory structures. Sexual maturity and/or pubertal delay occur depending on the sex and knockout. Male null FSH-R mice have reduced fertility but null LH-R males are sterile due to cryptorchid testes and deficient spermatogenesis. In null FSH-R females hormonal imbalances are due to deficient estrogen and hyperandrogenemia. LH-R deficient females have low estrogen and testosterone. Females in both knockouts display phenotypes such as obesity, bone deficiency, and changes in brain structure and function in addition to manifestation of different types of reproductive tract tumors. Both types of mice represent good models for testing hormone replacement therapy in different combinations. The FSH-R heterozygous females could also be useful for studying age-dependent phenotypes.

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References

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

    Article  PubMed  CAS  Google Scholar 

  2. Ahima, R. S., Dushay, J., Flier, S. N., Prabakaran, D., and Flier, J. S. (1997). J. Clin. Invest. 99, 391–395.

    Article  PubMed  CAS  Google Scholar 

  3. Aittomäki, K., Dieguez Lucena, J. L., Pakarinen, P., et al. (1995). Cell 82, 959–968.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  5. Balla, A., Danilovich, N., Yang, Y., and Sairam, M. R. (2003). Biol. Reprod. 69, 1281–1293.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. Carreau, S., Genissel, C., Bilinska, B., and Levallet, J. (1999). Int. J. Androl. 22, 211–223.

    Article  PubMed  CAS  Google Scholar 

  8. Danilovich, N., Babu, P. S., Xing, W., Gerdes, M., Krishnamurthy, H., and Sairam, M. R. (2000). Endocrinology 141, 4295–4308.

    Article  PubMed  CAS  Google Scholar 

  9. Danilovich, N., Roy, I., and Sairam, M. R. (2001). Endocrinology 142, 3673–3684.

    Article  PubMed  CAS  Google Scholar 

  10. Danilovich, N. and Sairam, M. R. (2002). Biol. Reprod. 67, 361–369.

    Article  PubMed  CAS  Google Scholar 

  11. Danilovich, N., Javeshghani, D., Xing, W., and Sairam, M. R. (2002). Biol. Reprod. 67, 370–378.

    Article  PubMed  CAS  Google Scholar 

  12. Danilovich, N., Roy, I., and Sairam, M. R. (2002). Endocrinology 143, 3618–3627.

    Article  PubMed  CAS  Google Scholar 

  13. Danilovich, N., Sairam, M. R., and Maysinger, D. (2003). Neuroreport 14, 1167–1622.

    Article  Google Scholar 

  14. Danilovich, N., Harada, N., Sairam, M. R., and Maysinger, D. (2003). Exp. Neurology 183, 559–572.

    Article  CAS  Google Scholar 

  15. Dierich, A., Sairam, M. R., Monaco, L., et al. (1998). Proc. Natl. Acad. Sci. USA 95, 13612–13617.

    Article  PubMed  CAS  Google Scholar 

  16. Gambacciani, M., Ciaponi, M., Cappagli, B., et al. (1997). J. Clin. Endocrinol. Metab. 82, 414–417.

    Article  PubMed  CAS  Google Scholar 

  17. Gambineri, A., Pelusi, C., Vicennati, V., Pagotto, U., and Pasquali, R. (2002). Int. J. Obes. Relat. Metab. Disord. 26, 883–896.

    Article  PubMed  CAS  Google Scholar 

  18. Grover, A., Sairam, M. R., Smith, C. E., and Louis Hermo, L. (2004). Biol. Reprod. 71, 117–129.

    Article  PubMed  CAS  Google Scholar 

  19. Grover, A., Smith, C. E., Gregory, M., Cyr, D. G., Sairam, M. R., and Hermo, L. (2005). Mol. Repro. Develop., in press.

  20. Hirst, R. C., Abel, M. H., Wilkins, V., et al. (2004). Reproduction 128, 43–52.

    Article  PubMed  CAS  Google Scholar 

  21. Huhtaniemi, I. T. and Themmen, A. P. N. (2005). Endocrine 26, 207–217.

    Article  PubMed  CAS  Google Scholar 

  22. Huhtaniemi, I., Zhang, F. P., Kero, J., Hamalainen, T., and Poutanen, M. (2002). Mol. Cell. Endocrinol. 187, 49–56.

    Article  PubMed  CAS  Google Scholar 

  23. Jegou, B., Le Gac, F., and de Kretser, D. M. (1982). Biol. Reprod. 27, 590–595.

    Article  PubMed  CAS  Google Scholar 

  24. Keri, R. A., Lozada, K. L., Abdul-Karim, F. W., Nadeau, J. H., and Nilson, J. H. (2000). Proc. Natl. Acad. Sci. USA 97, 383–387.

    Article  PubMed  CAS  Google Scholar 

  25. Krishnamurthy, H., Danilovich, N., Morales, C., and Sairam, M. R. (2000). Biol. Reprod. 62, 1146–1159.

    Article  PubMed  CAS  Google Scholar 

  26. Krishnamurthy, H., Suresh Babu, P., Morales, C. M., and Sairam, M. R. (2001). Biol. Reprod. 65, 522–531.

    Article  PubMed  CAS  Google Scholar 

  27. Krishnamurthy, H., Kats, R., Danilovich, N., Javeshghani, D., and Sairam, M. R. (2001). Biol. Reprod. 65, 1201–1207.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  30. Lei, Z. M., Zou, W., Mishra, S., Li, X., and Rao, Ch. V. (2003). Biol. Reprod. 68, 888–895.

    Article  PubMed  CAS  Google Scholar 

  31. 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 

  32. Oko, R. and Clermont, Y. (1990). In: Controls of sperm motility: biological and clinical aspects. Gagnon, C. (ed.). CRC Press Inc: Boca Raton, FL, pp. 3–27.

    Google Scholar 

  33. Pakarinen, P., Kimura, S., El-Gehani, F., Pelliniemi, L. J., and Huhtaniemi, I. (2002). Endocrinology 143, 4477–4482.

    Article  PubMed  CAS  Google Scholar 

  34. O’Shaughnessy, P. J., Dudley, K., and Rajapaksha, W. R. (1996). Mol. Cell. Endocrinol. 125, 169–175.

    Article  PubMed  CAS  Google Scholar 

  35. O’Shaughnessy, P. J., McLelland, D., and McBride, M. W. (1997). Biol. Reprod. 57, 602–608.

    Article  PubMed  CAS  Google Scholar 

  36. Rao, C. V. and Lei, Z. M. (2002). Mol. Cell. Endocrinol. 187, 57–67.

    Article  PubMed  CAS  Google Scholar 

  37. Risma, K. A., Clay, C. M., Nett, T. M., Wagner, T., Yun, J., and Nilson, J. H. (1995). Proc. Natl. Acad. Sci. USA 92, 1322–1326.

    Article  PubMed  CAS  Google Scholar 

  38. Risma, K. A., Hirshfield, A. N., and Nilson, J. H. (1997). Endocrinology 138, 3540–3547.

    Article  PubMed  CAS  Google Scholar 

  39. Sairam, M. R. and Krishnamurthy, H. (2001). Arch. Med. Res. 32, 601–608.

    Article  PubMed  CAS  Google Scholar 

  40. Sairam, M. R., Danilovich, N., and Lussier-Cacan, S. (2002). J. Reprod. Med. 47, 412–418.

    PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  42. Turgeon, J. L., McDonnell, D. P., Martin, K. A., and Wise, P. M. (2004). Science 304, 1269–1273.

    Article  PubMed  CAS  Google Scholar 

  43. Turner, R. T., Riggs, B. L., and Spelsberg, T. C. (1994). Endocr. Rev. 15, 275–300.

    Article  PubMed  CAS  Google Scholar 

  44. Xing, W., Krishnamurthy, H., and Sairam, M. R. (2003). Biochem. Biophys. Res. Commun. 312, 697–701.

    Article  PubMed  CAS  Google Scholar 

  45. Yarram, S. J., Perry, M. J., Christopher, T. J., et al. (2003). Endocrinology 144, 3555–3564.

    Article  PubMed  CAS  Google Scholar 

  46. Zhang, T., Guo, C.-X., Hu, Z.-Y., and Liu, Y.-X. (1997). Mol. Hum. Reprod. 3, 945–952.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  48. Li, X., Lei, Z. M., and Rao, Ch. V. (2000). In: Program of the Endocrine Society Annual Meeting, Abstract 259.

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Author notes

  1. Natalia Danilovich

    Present address: Kazakhstan Institute of Management, Economics & Strategic Research (KIMEP), 4 Abai Ave., 310, 480100, Almaty, Kazakhstan

Authors and Affiliations

  1. Molecular Reproduction Research Laboratory, Clinical Research Institute of Montréal, 110, avenue des Pins Ouest, H2W 1R7, Montréal, QC, Canada

    Natalia Danilovich & M. Ram Sairam PhD

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  1. Natalia Danilovich
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  2. M. Ram Sairam PhD
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Correspondence to M. Ram Sairam PhD.

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Danilovich, N., Sairam, M.R. Targeting gonadotropin receptor genes. Endocr 26, 219–226 (2005). https://doi.org/10.1385/ENDO:26:3:219

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  • DOI: https://doi.org/10.1385/ENDO:26:3:219

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