Estradiol enhances prostaglandin synthase activity in epithelial but not in stromal cells of human endometrium

Abstract

Exogenous estradiol (E 2) has been shown to elevate PGF 2α output by explants of human secretory endometrium and in monolayer cultures of glandular epithelial, but not of stromal cells isolated from endometrium. In this study, PGF 2α output was measured in each of these cultures in the presence of E 2 and the calcium ionophore A23187, added singly or in combination. The ionophore, known to liberate arachidonic acid (AA) by stimulating phospholipase activity, produced a calcium-dependent increase in PGF 2α output in the cultures of epithelial cells, whereas greater than additive effects were obtained with mixtures of E 2 and A23187. In contrast, PGF 2α levels were not elevated by A23187 in the stromal cell cultures even in medium supplemented with CaCl 2 or when E 2 was added. A calcium-dependent increase in PGF 2α output was also observed in fragments of secretory endometrium incubated with A23187. Effects on PGF 2α output by endometrial fragments incubated with E 2 and A23187 were essentially additive and intermediate between those of the two component cells types. Arachidonic acid produced similar increases in PGF 2α output in the epithelial and stromal cell cultures but only in the epithelial cell cultures was there greater utilization of AA in the presence of Ez. When mixtures of Ez and AA were added to the cultures of epithelial cells the increase in PGF 2α output was 2.5-fold greater than the sum of the increases elicited by E 2 or AA alone. In contrast, no enhancement of the AA effect by E 2 was observed in the stromal cell cultures. Extrapolation of these results from cell cultures to intact tissue suggests that the epithelium and not the stroma is the primary target for the effects of E 2 on PGF 2α output by secretory endometrium. The synergistic actions of E 2 and either AA, the obligatory precursor of PGF 2α, or A23187, an enhancer of AA release from phospholipid stores, point to a stimulatory effect of E 2 on prostaglandin synthase activity.