, Volume 10, Issue 2, pp 171–177

Pax6 is implicated in murine pituitary endocrine function

  • Cornelia A. Bentley
  • Miriam P. Zidehsarai
  • Justin C. Grindley
  • A. F. Parlow
  • Sara Barth-Hall
  • Veronica J. Roberts


Pax6, an evolutionarily conserved transcription factor, is expressed in the murine and zebrafish embryonic pituitary, but its role in pituitary development and endocrine function has not been described. To study the role of Pax6 in vivo, we examined Pax6 mutant mouse (SeyNeu) pituitaries. Mice homozygous for the SeyNeu mutation die at birth; therefore, we examined peptide hormone expression by the differentiated pituitary cell types as well as developmental marker expression in the intermediate and anterior lobes of the embryonic pituitary. GH- and PRL-immunopositive cells appear severely decreased in an outbred ICR background at embryonic d 17.5, although mRNA expression of these peptide hormones is present, as is expression of other pituitary markers. This suggests that pituitary cell types are able to differentiate in mutant embryos. To identify the cellular or physiologic mechanism responsible for less GH-and PRL-immunoreactivity in Pax6 mutant mice, we tested serum levels of GH and PRL. Pax6 homozygous mutant mice have GH serum levels one fifth that of controls at embryonic d 17.5, and one-third that of controls at postnatal d 0. PRL serum levels, which are very low during embryonic and neonatal stages, were below assay detection limits in both the wild-type and mutant groups. Taken together, these data suggest that Pax6 is not essential for pituitary differentiation, but rather functions to establish appropriate neonatal homeostatic levels of GH and PRL, possibly through regulation of translational or secretory mechanisms.

Key Words

Pax6 pituitary SeyNeu 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Roberts, R. C. (1967) Genet Res. 9, 121–122.CrossRefGoogle Scholar
  2. 2.
    Hill, R. E., Favor, J., Hogan, B. L. M, Ton, C. C. T., Saunders, G. F., Hanson, I. M., Prosser J., Jordan, T., Hastie, N. D., and Van Heyningen, V. (1991) Nature 354, 522–525.PubMedCrossRefGoogle Scholar
  3. 3.
    Glaser, T., Jepeal, L., Edwards, J. G., Young, S. R., Favor, J., and Maas, R. I. (1994),. Nature Genet. 7, 463–471.PubMedCrossRefGoogle Scholar
  4. 4.
    Hogan, B. L. M., Horsburgh, G., Cohen, J., Hetherington, C. M., Fisher, G., and Lyon, M. F. (1986). J. Embryol. Exp. Morph. 97, 95–110.PubMedGoogle Scholar
  5. 5.
    Matsuo, T., Osumi-Yamashita, N., Noji, S., Ohuchi, H., Koyama, E., Myokai, F., Matsuo, N., Taniguchi, S., Doi, H., Iseki, S., Ninomiya, Y., Fujiwara, M., Watanabe, T., and Eto, K. (1993), Nature Genet. 3, 299–304.PubMedCrossRefGoogle Scholar
  6. 6.
    Schmahl, W., Knowedlseder, M., Favor, J., and Davidson, D. (1993). Acta Neuropath. 86, 126–135.Google Scholar
  7. 7.
    St-Onge, L., Sosa-Pineda, B., Chowdhury, K., Mansourik, A., and Gruss, P. (1997) Nature 387, 406–409.PubMedCrossRefGoogle Scholar
  8. 8.
    Frohman, L. A. (1987) In Endocrinology and Metabolism, Felig, P., Baxter, J. D., Broadus, A. E. and Frohman, L. A., eds., McGraw-Hill Book Company, New York, pp. 252–273.Google Scholar
  9. 9.
    Walther, C., and Gruss, P. (1991) Development 113, 1435–1449.PubMedGoogle Scholar
  10. 10.
    Puschel, A. W., Gruss, P. and Westerfield, M. (1992) Development 114, 643–651.PubMedGoogle Scholar
  11. 11.
    Turque N., Plaza, S., Radvanyi F., Carriere, C., and Saule, S. (1994), Mol. Endocrinol. 8, 929–938.PubMedCrossRefGoogle Scholar
  12. 12.
    Schwind, J. (1928). Am. J. Anat. 41, 295–315.CrossRefGoogle Scholar
  13. 13.
    Ikeda, H., and Yoshimoto, T. (1991) Cell Tissue Res. 263, 41–47.PubMedCrossRefGoogle Scholar
  14. 14.
    Voss, J. W., and Rosenfeld, M. G. (1992) Cell 70, 527–530.PubMedCrossRefGoogle Scholar
  15. 15.
    Sornson, M. W., Wu, W., Dasen, J. S., Flynn, S. E., Norman, D. J., O'Connell, S. M., et al (1996), Nature 384, 327–333.PubMedCrossRefGoogle Scholar
  16. 16.
    Bodner, M., Castrillo, J. L., Theill, L. E, deerink, T., Ellisman, M., and Karin, M. (1988), Cell 50, 26–275.Google Scholar
  17. 17.
    Ingrahm, H. A., Chen, R., Mangalam, H. J., Elsholtz, H., Flynn, S. E., Lin, C. R., Simmons D. M., Swanson, L. W., and Rosenfeld, M. G. (1988), Cell 55, 519–529.CrossRefGoogle Scholar
  18. 18.
    Borrelli, E. (1994), Trends Genet. 10, 222–224.PubMedCrossRefGoogle Scholar
  19. 19.
    Quinn J. C., West, J. D., and Kaufman, M. H. (1997). Anat. Embryol. 196, 311–321.PubMedCrossRefGoogle Scholar
  20. 20.
    Zhadanov, A. B., Bertuzzi, S., Taira, M., Dawid, I. B., and Westphal, H. (1995), Dev. Dyn. 202, 354–364.PubMedGoogle Scholar
  21. 21.
    Thomas, P. Q., Johnson, B. V., Rathjen, J., and Rathjen, P. D. (1995). J. Biol. Chem. 270, 3869–3875.PubMedCrossRefGoogle Scholar
  22. 22.
    Hermesz, E., Mackem, S., and Mahon, K. A. (1996) Development 122, 41–52.PubMedGoogle Scholar
  23. 23.
    Mackenzie, A., Leeming, G. L., Jowett, A. K., Feguson, M. W. J., and Sharpe, P. T. (1991) Development 111, 269–285.PubMedGoogle Scholar
  24. 24.
    Yamanouchi, H., Kitauchi, S., and Shiino, M. (1997), Mol. Cell. Endocrinol. 134, 101–107.PubMedCrossRefGoogle Scholar
  25. 25.
    Quinn, J. C., West, J. D., and Hill, R. E. (1996), Genes Dev. 10, 435–446.PubMedCrossRefGoogle Scholar
  26. 26.
    Roberts, V. J., Barth, S., Meunier, H., and Vale, W. (1996), J. Comp. Neurol. 364, 473–493.Google Scholar
  27. 27.
    MacConell, L. A., Barth, S., and Roberts, V. J. (1996) Endocrinology 137, 2150–2158.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 1999

Authors and Affiliations

  • Cornelia A. Bentley
    • 1
    • 2
  • Miriam P. Zidehsarai
    • 1
  • Justin C. Grindley
    • 3
  • A. F. Parlow
    • 4
  • Sara Barth-Hall
    • 1
  • Veronica J. Roberts
    • 1
  1. 1.Department of Reproductive MedicineUniversity of California-San DiegoLa Jolla
  2. 2.Graduate Program in Biomedical SciencesVanderbilt University Medical CenterNashville
  3. 3.Department of Cell BiologyVanderbilt University Medical CenterNashville
  4. 4.Harbor-UCLA Medical CenterNational Hormone & Pituitary ProgramTorrance
  5. 5.Pepite Biology LaboratoryThe Salk InstituteLa Jolla

Personalised recommendations