In vitro inhibition with antiestrogens of estradiol effects on prostaglandin F2 alpha 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 F2 alpha (PGF2 alpha) production in ovariectomized rats, suggesting that in contrast to other steroid-initiated events, this effect on PGF2 alpha may not involve receptor-mediated transcription-dependent actions of E2. To eliminate indirect influences, the ability of antiestrogens to affect PGF2 alpha 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 PGF2 alpha output, tamoxifen and its metabolite trans-4-monohydroxytamoxifen acted as virtually pure antagonists, counteracting the E2 effect while failing to influence basal PGF2 alpha 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 PGF2 alpha production by both endometrial fragments and monolayers of epithelial cells.