Synergistic effects of corticotropin and insulin-like growth factor I on corticotropin receptors and corticotropin responsiveness in cultured bovine adrenocortical cells

Pretreatment of bovine adrenocortical cells with increasing concentrations of insulin-like growth factor I (IGF-I) for 3 days resulted in a dose dependent (ED50 congruent to 5 ng/ml) increment in Corticotropin (ACTH) receptors. Moreover, IGF-I pretreatment potentiated the effects of maximal active concentration of ACTH (10(-9) M) on its own receptors. Whereas ACTH (10(-9) M) or IGF-I (50 ng/ml) alone induced a 3- and 2.5-fold increase respectively in ACTH receptors, there was a 7.5 fold increase in the presence of the two peptides. This synergism between ACTH and IGF-I was also observed for the ACTH-induced cortisol response with an increase of 9-, 3- and 20-fold for cells pretreated with ACTH, IGF-I and the two peptides, respectively. However, the effects of both peptides on ACTH-induced cAMP production was only additive. The present results show that ACTH and IGF-I are potent stimulating factors on bovine adrenal cell differentiated functions and that the effects of both peptides are synergistic.