In vitro inhibition with antiestrogens of estradiol effects on prostaglandin F_2β production by human endometrium and endometrial epithelial cells

It has been previously reported that neither an antiestrogen, actinomycin D, nor cycloheximide inhibited estradiol (E₂)-stimulated elevations in uterine prostaglandin F_2α (PGF_2α production in ovariectomized rats, suggesting that in contrast to other steroid-initiated events, this effect on PGF_2α may not involve receptor-mediated transcription-dependent actions of E₂. To eliminate indirect influences, the ability of antiestrogens to affect PGF_2α output was reevaluated during incubations of human secretory endometrium and in cultures of epithelial cells derived from glands isolated from proliferative and secretory tissues. In these preparations, which respond to E₂ with marked elevations in PGF_2α output, tamoxifen and its metabolite trans-4-monohydroxytamoxifen acted as virtually pure antagonists, counteracting the E₂ effect while failing to influence basal PGF_2α output. Consistent with its effects on other estrogen-mediated end points, trans-4-monohydroxytamoxifen was at least 10 times more potent than tamoxifen, eliminating, at a 10⁻⁶ M concentration, almost completely the stimulatory effect of 10⁻⁸ M E₂ on PGF_2α production by both endometrial fragments and monolayers of epithelial cells.