INSULIN-LIKE GROWTH-FACTORS ENHANCE STEROIDOGENIC ENZYME AND CORTICOTROPIN RECEPTOR MESSENGER-RIBONUCLEIC-ACID LEVELS AND CORTICOTROPIN STEROIDOGENIC RESPONSIVENESS IN CULTURED HUMAN ADRENOCORTICAL-CELLS

In several species, including the human fetus, insulin-like growth fac tors (IGF-I and IGF-II) have been reported to modulate adrenal steroid ogenesis, thus contributing to adrenal cortical differentiation. In th e present study, we examined the long term effects of IGF-I and II on human adult adrenal fasciculata-reticularis cells cultured in a chemic ally defined medium and compared them to the effects of insulin, human GH, and ACTH. Treatment for 3 days with IGF-I or -II at nanomolar con centrations or with insulin at micromolar concentrations slightly incr eased the production of androstenedione, cortisol, and dehydroepiandro sterone about 1.5-fold over that by control cells. Moreover, the acute steroidogenic response to ACTH of cells pretreated with IGF-I, IGF-II , or insulin was 3- to 6-fold higher than that of control cells. For e ach hormone, these effects of IGF-I and -II were dose dependent betwee n 0.1-26 nmol/L (1-200 ng/mL). The secretion of androstenedione was mo re potently stimulated than that of dehydroepiandrosterone and cortiso l, and this effect was more clearly yielded by pretreatment with IGF-I I than with IGF-I or insulin. Human GH had no effect on these cells. I n cells treated with IGF-I or -II, the messenger ribonucleic acid (mRN A) levels of cytochrome P450 17 alpha-hydroxylase and of 3 beta-hydrox ysteroid dehydrogenase were increased, and the abundance of ACTH recep tor mRNA was also slightly enhanced, but the mRNA of cytochrome P450 c holesterol side-chain cleavage enzyme was unchanged. In conclusion, IG Fs enhance the steroidogenesis and ACTH responsiveness of human adreno cortical cells in culture. We speculate, that by this mechanism, IGFs may contribute to clinical states with hyperandrogenemia.