Abstract

To explore the mechanism for anti-ovulatory effects of blockade of preovulatory synthesis and action of progesterone, we focused on cyclooxygenase (COX)-2 induction and mitotic activity of granulosa cells in gonadotropins-treated rats. Treatment with RU486 (a progesterone receptor antagonist) or trilostane (a 3β-hydroxysteroid dehydrogenase inhibitor) just prior to or 4 h after human chorinonic gonadotropin (hCG) (hCG4h) decreased ovulation rates and circulating progesterone level. Human CG induction of immunoreactive COX-2 in the granulosa layer of mature Graafian follicles at hCG8h was reduced by RU486 treatment at hCG0h and trilostane treatment at hCG4h. RU486 treatment further attenuated ovarian prostaglandin E 2 (PGE 2) level significantly. Cell proliferative activity in mural granulosa layer of the inhibitors-treated follicles was significantly lower than in intact group. Obtained results show that inhibition of synthesis and action of progesterone caused attenuated COX-2/PGE 2 system and dysregulated mitotic response of granulosa cells, resulting in decreased ovulation.

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