INTERLEUKIN-1-BETA STIMULATES PROSTAGLANDIN-E(2) AND F(2-ALPHA) SYNTHESIS IN HUMAN OVARIAN GRANULOSA-CELLS IN CULTURE

To evaluate the roles of interleukin-1 (IL-1) in regulation of ovarian prostaglandin (PG) synthesis, we examined the effects of IL-1beta on PGE2, PGE2alpha, 6-keto-PGF1alpha and thromboxane (TX) B2 synthesis in cultures of human ovarian granulosa cells. Granulosa cells were obtai ned from hyperstimulated follicles in patients undergoing oocyte retri eval for in vitro fertilization-embryo transfer (IVF-ET). IL-1beta inc reased immunoreactive concentrations of PGE2 and PGF2alpha in culture medium in time- and dose-dependent manners. Concentration of PGE2 was significantly higher after 24 h incubation with 5 or more units/ml of IL-1beta, when compared to the control value obtained without IL-1beta (P < 0.05). Concentration of PGF2alpha was significantly higher after 8 h incubation with more than 2 units/ml of IL-1beta (P < 0.05). The increase in PGE2 was observed even in the presence of human chorionic gonadotropin (hCG), and blocked by indomenthacin, an inhibitor of cycl ooxygenase. During a 10 day incubation period, stimulatory effects of IL-1beta on PG synthesis were observed only on the first 2 days incuba tions. Concentrations of 6-keto-PGF1alpha and TXB2 were below our meas urement limits. This study demonstrated that IL-1beta stimulates PG sy nthesis in human ovarian granulosa cells in vitro. IL-1 seems to play an important role in regulating ovarian functions.