Inhibitory effect of somatomedin C/insulin-like growth factor I on adrenocorticotropin- or forskolin-induced steroidogenesis in isolated rat adrenocortical cells.

The effects of recombinant human somatomedin C/insulin-like growth factor (IGF-I) on the steroidogenic response of isolated rat adrenocortical cells to ACTH, forskolin, and (Bu)2cAMP were examined during short term incubations. The effect of IGF-I on cAMP production by cells stimulated with ACTH or forskolin was also examined. IGF-I inhibited ACTH-, forskolin-, and (Bu)2cAMP-induced corticosterone production in a concentration-dependent manner. IGF-I (30 ng/ml) also significantly inhibited ACTH-induced cAMP production. However, the peptide had no significant effect on forskolin-induced cAMP production. IGF-I suppressed ACTH-induced cAMP production both in the presence and absence of 3-isobutyl-1-methylxanthine, suggesting that IGF-I acts to inhibit the formation of cAMP rather than the stimulation of cAMP degradation. The observation that IGF-I inhibited steroidogenesis induced by (Bu)2cAMP strongly suggests that one site of inhibition is at some step(s) distal to cAMP formation. However, the inhibition of cAMP production after stimulation with ACTH also suggests a plasma membrane site of action for IGF-I in adrenocortical cells.