Changes of Adrenocortical Function and the Ovarian Contribution with Age

Dissociation of adrenal cortisol and androgen secretion occurs in elderly men and women. The postmenopausal ovary produces androgens; however, previous reports regarding adrenocortical function in postmenopausal women did not exclude the ovarian contribution to peripheral steroid levels. In the present study, changes in the ovarian contribution to adrenocortical function with age were determined by measuring peripheral concentrations of C19 and C21 steroids before and 2 weeks after ovariectomy. The rapid adrenocorticotropic hormone (ACTH) stimulation test (tetracosactide acetate, 0.25 mg i.v.) was performed, and the age-related difference in the response of steroid levels to ACTH stimulation was also determined in ovariectomized reproductive-age (mean age, 33.0 years, n=6) and postmenopausal women (mean age, 63.3 years, n=9) . After ovariectomy, the concentrations of pregnenolone, 17a-hydroxypregnenolone, progesterone, 17α-hydroxyprogesterone, dehydroepiandrosterone, and androstenedione in reproductive-age women decreased significantly to the levels in postmenopausal women. On the other hand, no significant changes in steroid levels before and after ovariectomy were observed in postmenopausal women. When changes in steroid levels in response to ACTH were compared, significant age-related reductions of dehydroepiandro-sterone, and androstenedione were observed with age but Δ4 and Δ5 C21 steroid levels in response to ACTH were preserved. These results suggest that C17-20 lyase activity decreases but 17a-hydroxylase is maintained for preservation of cortisol in response to ACTH. It is known that P450c17 is a single enzyme that catalyzes activity of both 17α-hydroxylase and C17-20 lyase. Therefore, changes in adrenal C17-20 lyase activity with age might affect adrenal androgen production.