Differential Effects of Estradiol, Arachidonic Acid, and A23187 on Prostaglandin F2αOutput by Epithelial and Stromal Cells of Human Endometrium*

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Abstract
Primary monolayer cultures of glandular epithelial cells and stromal cells derived from human endometrial curettings release similar amounts of prostaglandin F26 (PGF2.alpha.) to the incubation medium, but PGF2.alpha. output is significantly increased by estradiol (E2; 10-8M) only in epithelial cells. The differential responsiveness to estrogens of these two cell types was further demonstrated in the presence of exogenous arachidonic acid (AA), a PG precursor that markedly elevated PGF2.alpha. output by both epithelial and stromal cells. In epithelial cell cultures, the increases in PGF2.alpha. output obtained with mixtures of E2 and AA were about 2.5-fold greater than the sum of the increases elicited by E2 or AA alone. In contrast, the effects of AA in stromal cell cultures were not enhanced by E2. Addition of the calcium ionophore A23187 to cultures of epithelial cells resulted in a Ca2+-dependent increase in PGF2.alpha. output, which could be further augmented by E2 to levels almost twice the sum of those produced by each agonist alone. Unlike its effects on epithelial cells, A23187 did not significantly increase PGF2.alpha. levels in stromal cell cultures, regardless of the addition of Ca2+ (1.5 mM) or E2 (10-8 M) to the culture medium. These results suggest that the epithelia and not the stroma are the primary targets for the effects of E2 on PGE2.alpha. output by the endometrium. The synergistic effects of E2 and AA (the substrate for PG synthase) or of E2 and A23187 (a stimulator of phospholipase-mediated release of AA from phospholipid stores) on PGF2.alpha. production suggest that estrogens enhance PG production in epithelial cells by elevating PG synthase activity.