ESTRADIOL-17β STIMULATES DNA SYNTHESIS IN RAT GRANULOSA CELLS: ACTION MEDIATED BY TRANSFORMING GROWTH FACTOR-β

Abstract

Estradiol-17 beta is a mitogen in vivo for the proliferation of granulosa cells in the rat ovary. In this study we have shown that estradiol-17 beta acts on cultures of immature rat granulosa cells to stimulate DNA synthesis. DNA synthesis stimulated by estradiol-17 beta was enhanced by FSH. We have shown previously that transforming growth factor-beta (TGF-beta) stimulates DNA synthesis in rat granulosa cells in vitro and that this effect is augmented by FSH. The mitogenic action of estradiol-17 beta was mediated, at least in part, by a TGF-beta-like factor since in the presence of a neutralizing antibody to TGF-beta, DNA synthesis was attenuated. This conclusion was further supported by the novel finding that estradiol-17 beta stimulated the secretion of a TGF-beta-like factor by rat granulosa cells in culture. In summary, the evidence suggests that the actions of estradiol-17 beta and TGF-beta on DNA synthesis are interrelated, and that a TGF-beta-like factor mediates the mitogenic effects of estradiol-17 beta on rat granulosa cells.