INHIBITORY EFFECT OF SOMATOMEDIN-C INSULIN-LIKE GROWTH FACTOR-I ON ADRENOCORTICOTROPIN-INDUCED 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 re-sponse 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 pro-duction 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-isobu- tyl-l-methylxanthine, suggesting that IGF-I acts to inhibit the formation of cAMP rather than the stimulation of cAMP deg-radation. The observation that IGF-I inhibited steroidogenesis induced by (Bu)2cAMP strongly suggests that one site of inhi-bition 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. © 1990 by The Endocrine Society.