Insulin-like growth factor I (IGF I) induces cortisol production in bovine adrenocortical cells in primary culture

The effects of a physiological dose of IGF I (40 ng/ml ≈ 5 × 10⁻⁹ M) on steroidogenesis were studied in bovine adrenal fasciculata cells cultured in serum-free McCoy's medium. They were compared with those of a single dose of ACTH (0.25 ng/ml ≈ 10⁻¹⁰ M) at approximately the concentration inducing half-maximal stimulation. With IGF I, steroidogenesis commenced after 48 h culture and progressively increased throughout the 96-h test period. Expressed as stimulated level/control level ratios, glucocorticoid (cortisol + corticosterone) responses to IGF I after 4 days' culture (2.41 ± 0.20 (SEM) n = 9) were similar to those obtained with ACTH (2.59 ± 0.18, n = 9). A combination of the two peptides had a synergistic effect (5.95 ± 0.79, n = 5).

The cortisol/corticosterone ratio increased in the presence of IGF I from 1 ± 0.19 to 1.76 ± 0.45 (n = 7, P < 0.02), although less so than in the presence of ACTH (5.50 ± 0.98). Moreover, cortisol production was accompanied by adrostenedione production (2.36ng/10⁶ cells, n = 3) similar to that induced by ACTH (2.10 ng/10⁶ cells, n = 3). These findings together suggest stimulation of 17α-hydroxylase activity. Cell multiplication was unaffected by IGF I. [³H]Thymidine incorporation into DNA reached only 193% ± 17 (SEM) (n = 4) of control levels, whereas with ACTH it dropped to 60% ± 5.

Our findings show that IGF I alone has no mitogenic effect on adrenocortical cells in vitro, but that it is capable of inducing differentiated steroidogenesis.