Differentiation between the effects of IGF-1 and GH on PMSG-induced progesterone production by rat granulosa cells

The effects of insulin-like growth factor-1 (IGF-1) and growth hormone (GH) on pregnant mare serum gonadotropin (PMSG)-induced progesterone production by cultured granulosa cells have been studied. Rat granulosa cells were cultured in different concentrations of PMSG (0-100 mU/ml) plus or minus IGF-1 (4 nM) or GH (hGH, 2.5 or 10 nM) in the presence or absence of cortisol (2.4 micrograms/ml) and/or insulin (68 nM) in low (5 micrograms/ml) or high (50 micrograms/ml) concentrations of transferrin (TRF). IGF-1 augmented PMSG-induced progesterone production in both low and high TRF. The maximal increments were 6.6 and 4.5 times at 20 mU/ml PMSG respectively in low and high TRF. The enhancement by IGF-1 of PMSG-induced progesterone production was greater at low TRF concentrations. When cortisol was added in both low and high TRF, the enhancement by IGF-1 of PMSG-induced progesterone production was reversed and IGF-1 inhibited PMSG-induced progesterone production by 25.9% (low TRF) and 62.3% (high TRF) respectively. When a high dose of insulin was added instead of IGF-1, there was no obvious inhibition of the insulin stimulation by cortisol. In contrast, the IGF-1 inhibition in the presence of cortisol still existed in the presence of a high dose of insulin. These data indicate that insulin must have a direct effect of its own rather than simply acting as a surrogate IGF-1. GH inhibited PMSG-induced progesterone production by 37.2% and 61% respectively at 2.5 and 10 nM GH at low TRF concentration and 100 mU/ml PMSG.(ABSTRACT TRUNCATED AT 250 WORDS)