Dose-related action of estradiol on placental prostanoid prediction.

Prostanoids play an important role throughout all of pregnancy and during the initiation and progress of labor. The human placenta at term produces large quantities of prostanoids, yet little is known of the factors that regulate their biosynthesis. Herein, we report the effect of estradiol or estradiol and progesterone on the basal release of placental prostanoids from fresh human term placental explants using a perifusion system. The basal release of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), thromboxane (TxB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) increased about 50% from the fifth to the ninth hour in culture, while the release of 13, 14-dihydro-15-keto-PGF (PGFM) remained constant and hCG release decreased. The dose-related effect of estradiol (20-2,000 ng/ml) in the perifusing medium starting at the fifth hour of perifusion (i.e., the zero treatment time) effected no change in the release of TxB2, PGF2 alpha, PGFM or hCG. A biphasic action on the release of 6-keto-PGF1 alpha was observed, i.e. it was significantly decreased when incubated with 20 ng/ml of estradiol, but effected an increase after exposure to 200 ng/ml. The concomitant addition of progesterone (2,000 ng/ml) with estradiol (200 ng/ml) significantly inhibited the stimulatory action of estradiol at this dose. The release of PGF2 was inhibited in a dose-related fashion with increasing dose of estradiol. The addition of progesterone with estradiol (2,000 and 200 ng/ml, respectively) reversed the inhibition of PGE2 by estradiol alone. These data demonstrate that physiologic levels of estradiol affect 6-keto-PGF1 alpha and PGE2 release from the human term placenta, but do not significantly alter production of TxB2, PGFM or hCG under these conditions.