Insulin actions on ovarian steroidogenesis are not modulated by metformin

Metformin, an agent used in treatment of non-insulin-dependent diabetes mellitus, is believed to act by potentiating the effects of insulin on glucose metabolism. This study was designed to determine whether metformin affects the actions of insulin on ovarian steroidogenic capability. Rat thecal-interstitial (T-I) and granulosa (G) cells were cultured in chemically defined media for 144 h with or without gonadotrophins [luteinizing hormone (LH) at 100 ng/ml or follicle stimulating hormone (FSH) at 100 ng/ml], insulin (1 microgram/ml) and/or metformin (1 and 5 micrograms/ml). Production of testosterone and progesterone by T-I cells, and 17 beta-oestradiol and progesterone by G cells were assessed. Insulin potentiated LH-dependent stimulation of testosterone production by T-I cells and FSH-dependent stimulation of 17 beta-oestradiol production by G cells, but did not significantly affect progesterone production by T-I cells or G cells in the presence or absence of gonadotrophins. Metformin did not affect any of the actions of insulin on steroidogenesis. These results suggest that insulin may modulate ovarian steroidogenesis via a pathway separate from that modulating glucose metabolism. Actions of insulin on steroidogenesis are selective with regard to stimulation of specific aspects of steroidogenesis and do not simply amplify gonadotrophin effects.