Effects of Adrenocorticotropic Hormone, Human Chorionic Gonadotropin, and Insulin on Steroid Production by Human Adrenocortical Carcinoma Cells in Culture1

Adrenocortical carcinoma tissue removed from a mildly hirsute 16-year-old girl was cultured in order to assess steroidogenesis and responsiveness of the cells to adrenocorticotropic hormone (ACTH), human chorionic gonadotropin (HCG), and insulin. The cells in culture produced large amounts of androstenedione and testosterone; however, production of cortisol, which was initially high, decreased with time. No aldosterone, estrone, or estradiol was produced in vitro. Both monolayer cells maintained for 6 weeks and organ culture expiants maintained for over 3 days responded to ACTH (10"7 M)with increased production of androgens (testosterone, andro stenedione, dehydroepiandrosterone) but decreased production of cortisol as measured by radioimmunoassay of steroids in the culture media. Concomitant with decreased cortisol production was the enhanced formation of 11-deoxycortisol in cells exposed to ACTH, suggesting impaired 11ß-hydroxylation. Tissue ex posed to HCG (10~7 M) in organ culture showed an increase in androgen production over control levels, but no significant effect of HCG on glucocorticoid production was found. Tumor cells differed in their androgen response to ACTH and HCG, with enhanced adrenal androgens in the presence of ACTH and more gonadal-type androgens after exposure to HCG. Insulin expo sure had no effect on production of either androgen or glucocor ticoid by tumor tissue in organ culture. Thus, this adrenocortical carcinoma showed marked androgen production in culture which was enhanced in different ways by ACTH and HCG. 110-Hydroxylation was impaired with time in culture. No specific effect of insulin on steroidogenesis was noted.