INDUCTION OF STEROIDOGENIC ENZYME GENES BY INSULIN AND IGF-I IN CULTURED ADULT HUMAN ADRENOCORTICAL-CELLS

Insulin and the insulin-like growth factors (IGFs) have multiple roles in gene expression in steroidogenic cells. We investigated the regula tion of steroidogenic enzyme gene expression by insulin and IGF-I in p rimary cultures of human adrenocortical cells fron donors of ages 19-7 7 years. The effects of insulin and IGF-I observed here were independe nt of age and sex of the donor. After 5 days in serum-containing mediu m, cultures were exposed to insulin or IGF-I together with cyclic AMP analogs or ACTH in serum-free defined medium. Insulin and IGF-I at phy siological concentrations increased mRNA levels of 17 alpha-hydroxylas e and type II 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in the absence of cyclic AMP or ACTH. They had lesser effects on 21-hydroxyla se and cholesterol side-chain cleavage enzyme mRNA levels and were wit hout effect on 11 beta-hydroxylase mRNA. All steroidogenic enzyme mRNA s were strongly increased by cyclic AMP or ACTH, and this increase was potentiated by insulin or IGF-I. These effects of insulin and IGF-I w ere accompanied by decreases in the ratio of dehydroepiandrosterone/co rtisol synthesized from pregnenolone by the cultures. Induction of ste roidogenic enzyme genes in adult human adrenocortical cells by insulin and IGF-I is unlikely to occur by means of a cyclic AMP-dependent mec hanism. These data increase the evidence for an important regulation o f steroidogenesis by these hormones. (C) 1997 by Elsevier Science Inc.