Mifepristone attenuates human chorionic gonadotropin–induced extracellular signal–regulated kinase 1/2 phosphorylation, cyclooxygenase-2, and prostaglandin E 2 production in human granulosa luteal cells

Abstract

To elucidate the role of RU486 in regulating the function of granulosa luteal cells and its possible involvement in ovarian dysfunction. An in vitro study. University hospital. Our subjects were women under the age of 40 who were unable to get pregnant as a result of male-factor infertility. HCG and RU486 were added to cultured granulosa luteal cells; after incubation for 12 hours, the harvested cells were subjected to total mRNA and protein measurements. Reverse transcriptase-polymerase chain reaction, immunoblot assay, immunocytochemistry, and enzyme immunoassay were performed. RU486 attenuates hCG-induced cyclooxygenase-2 (COX-2) mRNA and protein expression and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and decreases the hCG-induced prostaglandin E2 (PGE2) production in a dose-dependent manner. RU486 treatment had no significant effect on COX-1 mRNA expression. Treatments using gonadotropins are able to induce ERK1/2 phosphorylation resulting in increased COX-2 protein expression and prostaglandin synthesis. RU486 attenuates the activation of ERK1/2, decreases the expression of COX-2, and affects PGE2 production by inhibiting hCG-induced COX-2 expression.