Effects of RU486 on cyclooxygenase-2 gene expression, prostaglandin F2alpha synthesis and ovulation in Xenopus laevis.

RU486 is a synthetic analog of progesterone and functions as a progesterone receptor antagonist. It binds to the progesterone receptor to prevent progesterone from occupying its receptor in many cellular systems. Early studies from our laboratory have shown that in Xenopus laevis ovarian follicles progesterone stimulates the expression of cyclooxygenase-2 (COX-2) gene which leads to a rapid increase in the production of prostaglandin F2alpha (PGF2alpha) and subsequent ovulation. In this study, we examined the effect of RU486 on the synthesis of COX-2 mRNA, production of PGF2alpha and ovulation in X. laevis. Ovarian tissue fragments were primed with human chorionic gonadotropin (hCG) and then incubated with progesterone (P4) alone or in the presence of varying concentrations of RU486 over a period of 12h. After the incubation ovulated oocytes were counted, COX-2 expression and synthesis of PGF2alpha were measured. Results demonstrated that RU486 attenuated the expression of COX-2 gene, reduced the synthesis of PGF2alpha, and inhibited ovulation in a dose-dependent manner. This finding suggests that progesterone receptor is an important regulator in the progesterone-cyclooxygenase-prostaglandin-mediated ovulation in amphibians.