Mechanism of the rapid antigonadotropic action of prostaglandins in cultured luteal cells

Abstract

A reproducible method for dissociation and culture of rat luteal cells is described. The concentration of LH [luteinizing hormone] required to produce half-maximal stimulation of progesterone secretion was 50 ng/ml. The effects of prostaglandin E2 (PGE2) and prostaglandin F2.alpha. (PGF2.alpha.) on basal and luteinizing hormone LH-stimulated progesterone production were examined. Both PG stimulated basal progesterone production but PGE2 was about twice as active, showing a 2-fold maximal stimulation at 0.75 .mu.M. When either PG was incubated simultaneously with LH, a dose-dependent inhibition of progesterone secretion occurred; PGF2.alpha. was 4 times more active than PGE2, showing 50% inhibition at a concentration of 40 .times. nM. Both PG are more active as antagonists than as agonists of LH with respect to progesterone secretion. PGF2.alpha. also inhibited LH-stimulated adenylate cyclase activity and cyclic[c]AMP accumulation. The block in progesterone secretion was reversed by addition of dibutyryl cAMP (1 mM) but not by theophylline (5 mM) alone. These data and the finding that PGF2.alpha. did not affect the specific binding activity of the LH receptor in intact luteal cells indicate that the rapid action of PG in luteal cells is due to a block of LH-dependent production of cAMP which results in a decrease in progesterone secretion.