Mammary Gland Development and the Prolactin Receptor

  • Nadine Binart
  • Christopher J. Ormandy
  • Paul A. Kelly
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 480)


Prolactin (PRL), synthesized by the anterior pituitary and to a lesser extent by numerous extrapituitary tissues, affects more physiological processes than all other pituitary hormones combined. This hormone is involved in >300 separate effects in various vertebrate species where its role has been well documented. The initial step in its action is the binding to a specific membrane receptor which belongs to the superfamily of class1cytokine receptors. The function of this receptor is mediated, at least in part, by two families of signaling molecules: Janus kinases and signal transducers and activators of transcription. PRL-binding sites have been identified in a number of cells and tissues of adult animals. Disruption of the gene for the PRL receptor has provided a new animal model with which to better understand the actions of PRL on mammary morphogenesis and mammary gland gene expression. The recent availability of genetic mouse models provides new insights into mammary developmental biology and how the action of a hormone at specific stages of development can have effects later in life on processes such as mammary development and breast cancer initiation and progression.

Key words

prolactin prolactin receptor 


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  1. 1.
    Neville, M.C. and Daniel, C.W., 1987, The Mammary Gland: Development regulation and function (New York: Plenum Press), pp 383–438.Google Scholar
  2. 2.
    Li, C.H., Dixon, J.S., Lo, T.B., Pankov, Y.M., and Schmidt, K.D., 1969, Amino acid sequence of ovine lactogenic hormone. Nature 224: 695–696.Google Scholar
  3. 3.
    Nicoll, C.S., Mayer, G.L., and Russell, S.M., 1986, Structural features of prolactins and growth hormones that can be related to their biological properties. Endocr. Rev. 7: 169–203.Google Scholar
  4. 4.
    Ben-Jonathan, N., Mershon, J.L., Allen, D.L., and Steinmetz, R.W., 1996, Extrapituitary prolactin: distribution, regulation, functions, and clinical aspects. Endocr. Rev. 17: 639–669.Google Scholar
  5. 5.
    Kelly, M.A., Rubinstein, M., Asa, S.L., Zhang, G., Saez, C., Bunzow, J.R., Allen, R.G., Hnasko, R., Ben-Jonathan, N., Grandy, D.K., and Low, M.J., 1997, Pituitary lactotroph hyperplasia and chronic hyperprolactinemia in dopamine D2 receptor-deficient mice. Neuron 19: 103–113.Google Scholar
  6. 6.
    Niall, H.D., Hogan, M.L., Sauer, R., Rosenblum, I.Y., and Greenwood, F.C., 1971, Sequences of pituitary and placental lactogenic and growth hormones: evolution from a primordial peptide by gene duplication. Proc. Natl. Acad. Sci. USA 68: 866–870.Google Scholar
  7. 7.
    Miller, W.L. and Eberhardt, N.L., 1983, Structure and evolution of the growth hormone gene family. Endocr. Rev. 4: 97–130.Google Scholar
  8. 8.
    Goffn, V., Shiverick, K.T., Kelly, P.A., and Martial, J.A., 1996, Sequence-function relationships within the expanding family of prolactin, growth hormone, placental lactogen and related proteins in mammals. Endocr. Rev. 17: 385–410.Google Scholar
  9. 9.
    Kacsoh, B., Veress, Z., Toth, B.E., Avery, L.M., and Grosvenor, C.E., 1993, Bioactive and immunoreactive variants of prolactin in milk and serum of lactating rats and their pups. J. Endocrinol. 138: 243–257.Google Scholar
  10. 10.
    Nagy, E. and Berczi, I., 1991, Hypophysectomized rats depend on residual prolactin for survival. Endocrinology 128: 2776–2784.Google Scholar
  11. 11.
    Imagawa, W., Yang, J., Guzman, R., and Nandi, S., 1994, Control of mammary development. In The Physiology of Reproduction. E. Knobil, J.D. Neil, L.L. Ewing, G.S. Greenwald, C.L. Markert, and D.W. Pfaff, eds. (New York: Raven Press), pp. 1033–1063.Google Scholar
  12. 12.
    Horseman, N.D., Zhao, W., Montecino-Rodriguez, E., Tanaka, M., Nakashima, K., Engle, S.J., Smith, F., Markoff, E., and Dorshkind, K., 1997, Defective mammopoiesis, but normal hematopoiesis, in mice with a targeted disruption of the prolactin gene. EMBO J. 16: 6926–6935.Google Scholar
  13. 13.
    Ormandy, C.J., Camus, A., Barra, J., Damotte, D., Lucas, B.K., Buteau, H., Edery, M., Brousse, N., Babinet, C., Binart, N., and Kelly, P.A., 1997, Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse. Genes Dev. 11: 167–178.Google Scholar
  14. 14.
    Ormandy, C.J., Binart, N., and Kelly, P.A., 1997, Mammary gland development in prolactin receptor knockout mice. J. Mammary Gland. Biol. Neopl. 2: 355–364.Google Scholar
  15. 15.
    Brisken, C., Kaur, S., Chavarria, T.E., Binart, N., Sutherland, R.L., Weinberg, R.A., Kelly, P.A., and Ormandy, C.J., 1999, Prolactin controls mammary gland development via direct and indirect mechanisms. Dev. Biol. 210: 96–106.Google Scholar
  16. 16.
    Lydon, J.P., DeMayo, F. J., Funk, C.R., Mani, S.K., Hughes, C.A., Montgomery, C.A., Shyamala, G., Conneely, O.M., and O’Malley, B.W., 1995, Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Genes Dev. 9: 2266–2278.Google Scholar
  17. 17.
    Korach, K.S., 1994, Insights from the study of animals lacking functional estrogen receptor. Science 266: 1524–1527.Google Scholar
  18. 18.
    Liu, X., Robinson, G.W., Wagner, K.U., Garrett, L., Wynshaw-Boris, A., and Hennighausen, L., 1997, Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes Dev. 11: 179–186.Google Scholar
  19. 19.
    Udy, G.B., Towers, R.P., Snell, R.G., Wilkins, R.J., Park, S.H., Ram, P.A., Waxman, D.J., and Davey, H.W., 1997, Requirement of Stat5b for sexual dimorphism of body growth rates and liver gene expression. Proc. Natl. Acad. Sci. USA 94: 7239–7244.Google Scholar
  20. 20.
    Toscani, A., Mettus, R.V., Coupland, R., Simpkins, H., Litvin, J., Orth, J., Hatton, K.S., and Reddy, E.P., 1997, Arrest of spermatogenesis and defective breast development in mice lacking A-myb. Nature 386: 713–717.Google Scholar
  21. 21.
    Fantl, V., Stamp, G., Andrews, A., Rosewell, I., and Dickson, C., 1995, Mice lacking cyclin D 1 are small and show defects in eye and mammary gland development. Genes Dev. 9: 2364–2372.Google Scholar
  22. 22.
    Jones, F.E., Jerry, D.J., Guarino, B.C., Andrews, G.C., and Stem, D.F., 1996, Heregulin induces in vivo proliferation and differentiation of mammary epithelium into secretory lobuloalveoli. Cell Growth Differ. 7: 1031–1038.Google Scholar
  23. 23.
    Krane, I.M. and Leder, P., 1996, NDF/heregulin induces persistence of terminal end buds and adenocarcinomas in the mammary glands of transgenic mice. Oncogene 12: 1781–1788.Google Scholar
  24. 24.
    Yang, Y., Spitzer, E., Meyer, D., Sachs, M., Niemann, C., Hartmann, G., Weidner, K.M., Birchmeier, C., and Birchmeier, W., 1995, Sequential requirement of hepatocyte growth factor and neuregulin in the morphogenesis and differentiation of the mammary gland. J. Cell Biol. 131: 215–226.Google Scholar
  25. 25.
    Sicinski, P., Donaher, J.L., Parker, S.B., Li, T., Fazeli, A., Gardner, H., Haslam, S.Z., Bronson, R.T., Elledge, S.J., and Weinberg, R.A., 1995, Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell 82: 621–630.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Nadine Binart
    • 1
  • Christopher J. Ormandy
    • 2
  • Paul A. Kelly
    • 1
  1. 1.Faculté de Médecine NeckerINSERM Unité 344 - Endocrinologie MoléculaireParis CedexFrance
  2. 2.Cancer Research ProgramGarvan Institute of Medical ResearchSydneyAustralia

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