PROGESTERONE-RECEPTOR REPRESSION BY ESTROGENS IN RAT UTERINE EPITHELIAL-CELLS

Measurements performed using cell lines or animal tissues have shown t hat the progesterone receptor (PR) can be induced by estrogens. By use of immunohistochemistry we studied the effects of estrogens on the PR levels in the individual cell types of the target organs uterus and b reast. In the uteri of rats, ovariectomy induced a decrease in PR immu noreactivity within the myometrium and outer stromal cell. layers. In contrast, in the uterine luminal and glandular epithelium and surround ing stromal cell layers the PR immunoreactivity was significantly enha nced. The same picture emerged when intact rats were treated with the pure estrogen receptor antagonist, ZM 182780 (10 mg/kg/d). Treatment o f ovariectomized rats with estradiol resulted in high PR levels in the myometrium and stroma cells but low PR immunoreactivity in the epithe lial cells. The ER-mediated repression of the PR immunoreactivity was evidently restricted to the uterine epithelium, as we found that in th e epithelial cells of the mammary gland and in cells of N-nitrosomethy lurea-induced mammary carcinomas the PR expression was induced by estr ogens and was blocked by the pure antiestrogen ZM 182780. These result s clearly show that in the rat the activated ER induces diverging effe cts on PR expression in different cell types even within the same orga n. (C) 1997 Elsevier Science Ltd. All rights reserved.