THE EFFECT OF DEXAMETHASONE ON CRH AND PROSTANOID PRODUCTION FORM HUMAN TERM PLACENTA

The human placenta at term produces large quantities of corticotropin releasing hormone (CRH) and prostanoids: These hormones play an import ant role in the maintenance of pregnancy and the initiation and progre ss of labor; yet little is known of factors affecting their regulation and the interrelationship of CRH and prostanoid production. In these studies we have investigated the effect of dexamethasone on the produc tion of CRH and prostanoids from fresh human term placental tissues. T he basal release oi prostaglandin E-2 (PGE(2)), prostaglandin F-2 alph a (PGF(2 alpha)), thromboxane B-2 (TxB(2)) and 6-keto-prostaglandin F- 1 alpha (6-keto-PGF(1 alpha)) from human term placental explants incre ased from the fifth hour in culture, while the release of 13,14-dihydr o-15-keto-PGF(2 alpha) (PGFM) was not significantly changed during thi s period. The addition of dexamethasone (10(-8) M) to the perifusing m edium resulted in a rapid and dramatic inhibition of PGE(2), PGF(2 alp ha), PGFM, TxB(2) and 6-keto-PGF(1 alpha) release. On the other hand, CRH release was not significantly changed throughout the seven hours o f incubation with dexamethasone. These data demonstrate that glucocort icoids at physiologic concentrations can inhibit human term placental prostanoid production and thus glucocorticoid production may play an i mportant role in the physiological regulation of placental prostanoid production in the human placenta. However, dexamethasone did not alter CRH release, demonstrating that the inhibition of placental prostanoi ds by dexamethasone is not a CRH mediated event.