Polarized rat uterine epithelium in vitro: constitutive expression of estrogen-induced proteins

The hormonal responsiveness of immature rat primary uterine epithelial (UE) cells, cultured in a serum-free, phenol red-free defined medium, was examined under conditions which allowed the UE cells to reestablish their polarized phenotype. In the absence of estradiol and phenol red UE cells proliferated to confluence, achieving cell densities equal to those reached by UE cells cultured in the presence of estradiol. The expression of marker proteins, characteristic of the in vivo response of the uterus to estrogen, i.e. the adhesion molecule cell CAM 105, complement component C3, the secretory component of the immunoglobulin A receptor, and keratan sulfate proteoglycan, by polarized cultures of UE cells proved to be independent of estrogen in vitro. Polarized UE cells required the presence of estrogen to maintain integrity of their monolayer and did exhibit a dose-dependent response to estradiol in vitro in terms of cell growth (hypertrophy) and the secretion of two proteins not previously described as estrogen response markers. UE cell secretion, in particular apical secretion, was stimulated by estradiol but not by progesterone, dexamethasone, or testosterone. Progesterone failed to down-regulate the polarized UE cell responses to estradiol. Collectively, these observations suggest that many of the responses which nominally characterize the action of estrogen on the UE cell in vivo are likely to be initiated by agents other than estrogen, e.g. growth factors.