Hormonal effects of PGF_2α output by cultures of epithelial and stromal cells in human endometrium

Estradiol stimulation and progesterone inhibition of human uterine PGF_2α production were studied using in vitro preparations of endometrial tissue and cells. Measurement of PGF_2α levels in media from primary cultures of glandular epithelia and stoma revealed that basal outputs were similar in both cell types but could be increased by estradiol only in epithelial cells. Tamoxifen (Tam) and trans-4-hydroxy tamoxifen (OHTam) did not affect basal PGF_2α outputs by secretory endometrium in organ culture and by monolayer cultures of epithelial cells, but counteracted the stimulatory effects of estradiol in both systems. The almost pure antiestrogenic activity exhibited by OHTam was at least 10 times greater than that of Tam, suggesting that the estrogen-stimulated increases in uterine PGF_2α output are mediated by specific estrogen receptors. Fragments of endometrium also released lipocortin, a phospholipase A₂-inhibiting protein believed to mediate inhibitory effects of glucocorticoids on prostaglanclin production in several types of cells. Although dexamethasone increased lipocortin and decreased PGF_2α output in secretory endometria in vitro, progesterone inhibited both lipocortin and PGF_2α output. The mechanisms by which P inhibits PGF_2α production remain to be elucidated.