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 obtained from hyperstimulated follicles in patients undergoing oocyte retrieval for in vitro fertilization-embryo transfer (IVF-ET). IL-1beta increased 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 cyclooxygenase. During a 10 day incubation period, stimulatory effects of IL-1beta on PG synthesis were observed only on the first 2 days incubations. Concentrations of 6-keto-PGF1alpha and TXB2 were below our measurement limits. This study demonstrated that IL-1beta stimulates PG synthesis in human ovarian granulosa cells in vitro. IL-1 seems to play an important role in regulating ovarian functions.