Leptin inhibits gonadotrophin-stimulated granulosa cell progesterone production by antagonizing insulin action

Recent evidence has demonstrated that expression of leptin and leptin recep tors is expected in the human ovary, and that leptin alters ovarian steroid ogenesis in animal models, This study was designed to determine whether lep tin modulates basal, gonadotrophin-, and insulin-stimulated progesterone pr oduction by human luteinized granulosa cells (GC). GC were recovered from f ollicular aspirates obtained during transvaginal ultrasound-guided oocyte r etrieval for in-vitro fertilization-embryo transfer, and cultured in define d medium with various combinations of chorionic gonadotrophin (HCG; 0 or 10 0 ng/ml), insulin (0-30 mu g/ml), and leptin (0-100 ng/ml), Progesterone co ncentrations in media were determined at various time points (2 h to 6 days ). Leptin time- and dose-dependently inhibited (P < 0.05) HCG-stimulated pr ogesterone production by human luteinized GC, but did not alter basal stero idogenesis, Moreover, the inhibitory effect of leptin on gonadotrophin-stim ulated progesterone production was only manifested in the presence of insul in. Leptin suppression of insulin-supported steroidogenesis was also time- and dose-dependent. We conclude that leptin inhibits gonadotrophin-stimulat ed GC progesterone production apparently by antagonizing insulin action. Le ptin suppression of progesterone production by human luteinized GC is consi stent with recent data from animal models, and supports the possible role o f leptin as a regulator of human ovarian function.