Adrenarche: Changing Adrenal Response to Adrenocorticotropin*

Abstract

The hypothesis that adrenarche results from an altered biosynthetic response to ACTH was tested. Adrenarche is the maturational increase in the production of adrenal 17-ketosteroids, particularly dehydroepiandrosterone (DHA) and DHA-sulfate (DHAS). Apparent steroidogenic efficiency was estimated from relationships between plasma steroid intermediates after administering ACTH-(1-24). ACTH testing was performed after giving a bedtime dose of dexamethasone to suppress the early morning ACTH surge. Three groups of patients were studied: 6 prepubertal children, 10 females with isolated adrenarche and 8 normal adult females in the follicular phase of their menstrual cycles. Prepubertal DHAS was 11, adrenarchal 105 and adult 208 .mu.g/dl. Adults had 5-fold greater DHA and .apprx. 2-fold greater androstenedione (AD) and 17-hydroxyprogesterone (17-PROG) than prepubertal children. Overnight dexamethasone suppression led to reduction of most steroids in most groups. Thirty minutes after a 10-.mu.g ACTH bolus, prepubertal children''s DHA rose 32, AD 15, 17-hydroxypregnenolone (17-PREG) 229 and 17-PROG 99 ng/dl; adrenarchal children''s DHA rose 236, AD 17, 17-PREG 298 and 17-PROG 96 ng/dl; and adult women''s DHA rose 665, AD 32, 17-PREG 924 and 17-PROG 60 ng/dl. The increments in DHA and 17-PREG levels between successive groups were the most significant changes. DHAS did not rise. The 17-PROG response to ACTH of the adult women was slightly less (P < 0.05) than that of the prepubertal children, despite increasing amounts of the precursor, 17-PREG, and the AD response was slightly greater (P < 0.05). After subsequent ACTH infusion DHAS did not rise in prepubertal children but rose 23 .+-. 5 .mu.g/dl in the adrenarchal and 27 .+-. 5 .mu.g/dl in the adult groups (P < 0.025). Most other differences among groups were preserved. The increased DHA of adrenarche apparently arises from a combination of changes in the response to ACTH; more of the precursor 17-PREG is available, the percentage of 17-PREG converted to DHA increases as the result of an apparent improvement of lyase efficiency, and DHA is less efficiently converted to AD because of an apparent decrease in .DELTA.5-3.beta.-hydroxysteroid dehydrogenase efficiency. The resultant increase in DHA after ACTH, together with acquisition of sulfokinase activity by the adrenal, could underly the adrenarchal rise in DHAS. Most of these changes probably result from development of the zona reticularis.