Mifepristone attenuates human chorionic gonadotropin-induced extracellular signal-regulated kinase 1/2 phosphorylation, cyclooxygenase-2, and prostaglandin E2 production in human granulosa luteal cells

Objective: To elucidate the role of RU486 in regulating the function of granulosa luteal cells and its possible involvement in ovarian dysfunction. Design: An in vitro study. Setting: University hospital. Patient(s): Our subjects were women under the age of 40 who were unable to get pregnant as a result of male-factor infertility. Intervention(s): 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. Main Outcome. Measure(s): Reverse transcriptase-polymerase chain reaction, inummoblot assay, immunocytochemistry, and enzyme immunoassay were performed. Result(s): 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 E-2 (PGE(2)) production in a dose-dependent manner. RU486 treatment had no significant effect on COX-I mRNA expression. Conclusion(s): 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.