Adrenarche: Physiology, Biochemistry and Human Disease

Richard J. Auchus; William E. Rainey


Clin Endocrinol. 2004;60(3) 

In This Article


Adrenarche is an enigmatic phenomenon that occurs only in human beings and some Old World monkeys. The biochemical hallmark of adrenarche is accelerated DHEA-S production by an expanding adrenal zona reticularis, and these cells are ideally suited for robust DHEA-S production. The concerted actions of CYP11A, CYP17 and SULT2A1, all of which are abundant in the reticularis cells, conspire to drive steroidogenesis efficiently to DHEA-S. DHEA-S production is further expedited by optimal levels of the cofactor proteins CPR and cytochrome b 5, which enhance the catalytic efficiency of the 17,20-lyase activity of CYP17. The absence of the competing enzyme 3βHSD ensures that nascent pregnenolone is almost exclusively metabolized via the Δ5-pathway to DHEA-S. Abnormalities in the timing and intensity of adrenarche are associated with insulin resistance and PCOS, and vigorous DHEA-S production may in part contribute to the increased cardiovascular risk borne by PCOS patients. The proximal signal for adrenarche remains unknown, although some biochemical clues to the process of adrenarche are being elucidated.

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