Insulin enhances ACTH-stimulated androgen and glucocorticoid metabolism in hyperandrogenic women.

Objective: In hyperandrogenic women, hyperinsulinemia amplifies 17a-hydroxycorticosteroid intermediate response to ACTH, but it does not alter serum cortisol or androgen response to stimulation. Aim of the study was to assess whether insulin may determine absolute changes in either basal or ACTH-stimulated adrenal steroidogenesis in these subjects. Research Design and Methods: Twelve young hyperandrogenic women were submitted on 2 separate days to an 8h-hyperinsulinemic (80 mU/m2 x min) euglycemic clamp, and to a 8h-saline infusion. In the second half of both protocols a 4h-ACTH infusion (62.5 mg/h) was carried out. Serum cortisol, progesterone, 17a-hydroxyprogesterone, 17a-hydroxypregnenolone, dehydroepiandrosterone and androstenedione were measured at basal and during the protocols. Absolute adrenal hormones secretion was quantified by measuring C19 and C21 steroid metabolites in urine collected after the first 4h of insulin or saline infusion, and after the subsequent 4h of concurrent ACTH infusion.Results: During insulin infusion ACTH-stimulated 17a-hydroxypregnenolone and 17a-hydroxyprogesterone levels were significantly higher than during saline infusion. No significant differences in cortisol and androgen response to ACTH were found between the protocols. Nevertheless, urinary excretion of ACTH-stimulated C19 and C21 steroid metabolites were significantly higher during hyperinsulinemia than at basal insulin levels (both p<0.005). Changes in steroid metabolites molar ratios suggested a stimulation by insulin of 5a-reductase activity.Conclusions: These in vivo data support the hypothesis that insulin acutely enhances ACTH effects on both the androgen and glucocorticoid pathways.