Is Estrogen a Cellular Signal for Female Genital Tract Epithelium?

  • Howard A. Bern


In vivo, the vagina and uterus, and their respective epithelial linings, are considered to be estrogen target structures. As a result of classical endocrinological studies, their dependence on estrogen for growth and differentiation is considered axiomatic. In vitro, primary cultures of epithelial cells from the vagina and uterus, grown in collagen gel matrix in a serum-free medium, proliferate independently of the presence of added estrogen. Addition of estrogen to these primary cultures does not stimulate epithelial cell proliferation, even in suboptimal conditions, but rather retards their growth. The estrogen receptor system of these cultured cells appears to be functionally intact, and the cells respond to estrogen addition by specific product synthesis (progestin receptors). Thus, estrogen has a direct modulative effect on cultured vaginal and uterine epithelia, but estrogen is not a directly-acting mitogen for these cells. It appears that stromal and possibly organismal factors are essential synergists and/or mediators for estrogen’s well-known mitogenic effect on female genital epithelia in vivo. Several alternative pathways for estrogen action on female genital epithelia are suggested.


Vaginal Epithelium Uterine Epithelium Uterine Epithelial Cell Progestin Receptor Vaginal Epithelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Buckley, A., Davidson, J.M., Kamerath, C.D., Wolt, T.B., and Woodward, S.C., Sustained release of epidermal growth factor accelerates wound repair, Proc. Natl. Acad. Sci. USA, 82:7340 (1985).PubMedCrossRefGoogle Scholar
  2. 2.
    Cooke, P.S., Uchima, F.-D.A., Fujii, D.K., Bern, H.A., and Cunha, G.R., Restoration of normal morphology and estrogen responsiveness in cultured vaginal and uterine epithelia transplanted with stroma, Proc. Natl. Acad. Sci. USA, 83:2109 (1986).PubMedCrossRefGoogle Scholar
  3. 3.
    Cunha, G.R., Stromal induction and specification of morphogenesis and cytodifferentiation of the epithelia of the Mullerian ducts and urogenital sinus during development of the uterus and vagina in mice, J. Exp. Zool., 196:361 (1976).PubMedCrossRefGoogle Scholar
  4. 4.
    Cunha, G.R. and Fujii, H., Stromal-parenchymal interactions in normal and abnormal development of the genital tract, In: Developmental Effects of Diethylstilbestrol (DES) in Pregnancy, A.L. Herbst and H.A. Bern, (eds.), Thieme-Stratton, New York (1981).Google Scholar
  5. 5.
    Gilchrest, B.A., Karassik, R.L., Wilkins, L.M., Vrabel, M.A., and Maciag, T., Autocrine and paracrine growth stimulation of cells derived from human skin, J. Cell. Physiol., 117:235–240.Google Scholar
  6. 6.
    Iguchi, T., Uchima, F.-D.A., Ostrander, P.L., and Bern, H.A., Growth of normal mouse vaginal epithelial cells in and on collagen gels, Proc. Natl. Acad. Sci. USA, 80:3743 (1983).PubMedCrossRefGoogle Scholar
  7. 7.
    Iguchi, T., Uchima, F.-D.A., Ostrander, P.L., Hamamoto, S.T., and Bern, H.A., Proliferation of normal mouse uterine luminal epithelial cells in serum-free collagen gel culture, Proc. Japan Acad., 61B:292 (1985).Google Scholar
  8. 8.
    Iguchi, T., Uchima, F.-D.A., and Bern, H.A., Growth of mouse vaginal epithelial cells in culture: effect of sera and supplemented serum-free media. In Vitro Cell. Devel. Biol., 23:535 (1987).CrossRefGoogle Scholar
  9. 9.
    Imagawa, W., Tomooka, Y., and Nandi, S., Serum-free growth of normal and tumor mouse mammary epithelial cells in primary culture, Proc. Natl. Acad. Sci. USA, 79:4074 (1982).PubMedCrossRefGoogle Scholar
  10. 10.
    Inaba, T., Wiest, W.G., Strickler, R.C., and Mori, J., Augmentation of the response of mouse uterine epithelial cells to estradiol by uterine stroma, Endocrinology, 123:1253 (1988).PubMedCrossRefGoogle Scholar
  11. 11.
    Knabbe, C., Lippman, M.E., Wakefield, L.M., Flanders, K.C., Kasid, A., Derynck, R., and Dickson R.B., Evidence that transforming growth factor-0 is a hormonally regulated negative growth factor in human breast cancer cells, Cell, 48:417 (1987).PubMedCrossRefGoogle Scholar
  12. 12.
    Shafie, S.M., Estrogen and the growth of breast cancer: new evidence suggests indirect action, Science, 209:701 (1980).PubMedCrossRefGoogle Scholar
  13. 13.
    Sirbasku, D.A., Estrogen induction of growth factors specific for hormone-responsive mammary, pituitary, and kidney tumor cells, Proc. Natl. Acad. Sci. USA, 75:3786 (1978).PubMedCrossRefGoogle Scholar
  14. 14.
    Sirbasku, D.A., Ikeda, T., and Danielpour, D., Characterization of endocrine and autocrine mammary tumor cell growth factors, In: Growth and Differentiation of Cells in Defined Environment, H. Murakami., (eds.), Springer-Verlag, Berlin (1985).Google Scholar
  15. 15.
    Soto, A.M. and Sonnenschein, C., The role of estrogens on the proliferation of human breast tumor cells (MCF-7), J. Steroid Biochem., 23:87 (1985).PubMedCrossRefGoogle Scholar
  16. 16.
    Soto, A.M. and Sonnenschein, C., Cell proliferation of estrogen-sensitive cells: The case for negative control, Endocrine Rev., 8:44–52 (1987).CrossRefGoogle Scholar
  17. 17.
    Sumida, C., Lecerf, F., and Pasqualini, J.R., Control of progesterone receptors in fetal uterine cells in culture: effects of estradiol, progestins, antiestrogens, and growth factors, Endocrinology, 122:3 (1988).PubMedCrossRefGoogle Scholar
  18. 18.
    Tsai, P.-S., Estrogen modulation of growth of mouse vaginal epithelium in cell and organ cultures, M.A. thesis in Zoology, University of California, Berkeley (1989).Google Scholar
  19. 19.
    Uchima, F.-D.A., Unpublished.Google Scholar
  20. 20.
    Uchima, F.-D.A., Edery, M., Iguchi, T., Larson, L., and Bern, H.A., Growth of mouse vaginal epithelial cells in culture: Functional integrity of the estrogen receptor system and failure of estrogen to induce proliferation. Cancer Lett., 35:227–235 (1987).PubMedCrossRefGoogle Scholar
  21. 21.
    Yang, J. and Nandi, S., Growth of cultured cells using collagen as substrate, Inter. Rev. Cytology, 81:249 (1983).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Howard A. Bern
    • 1
  1. 1.Department of Integrative Biology and Cancer Research LaboratoryUniversity of CaliforniaBerkeleyUSA

Personalised recommendations