Adrenarche: Physiology, Biochemistry and Human Disease

Summary and Introduction

Adrenarche refers to the onset of dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) production from the adrenal zona reticularis that can be detected at around 6 years of age. The phenotypic result of adrenarche is pubarche or the development of axillary and pubic hair that occurs in both girls and boys at about age 8. The phenomenon of adrenarche is unique to human beings and to some Old World primates, and a reversal of adrenarche appears to occur in the ageing process. Premature and exaggerated adrenarche can be indicative of future onset of adult diseases, thus increasing the clinical relevance of adrenarche. The physiological triggers of adrenarche and the role(s) of DHEA-S remain speculative. However, the biochemical pathways that define adrenarche have been characterized in detail, and the appearance of key enzymes and cofactors in the adrenal zona reticularis track with the progression of adrenarche. This article reviews the clinical manifestations of adrenarche, the biochemistry of the enzymes involved in DHEA-S production, and the cell biology of the adrenal zona reticularis.

Glucocorticoids and mineralocorticoids secreted by the adrenal glands are essential for the maintenance of vascular tone and carbohydrate metabolism or of blood volume and sodium balance, respectively. The testes and ovaries, by contrast, generate the sex steroids that are required for gametogenesis, secondary sexual characteristics and reproduction. However, the adrenal glands of adult human beings secrete generous quantities of the C₁₉ steroids dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S). Neither DHEA nor DHEA-S activate the androgen receptor, but in peripheral tissues they act as precursors for the potent androgens testosterone and dihydrotestosterone. The onset of DHEA-S production from the adrenal zona reticularis leads to the phenomenon of adrenarche. Adrenarche occurs only in human beings and some Old World primates, such as the chimpanzee (Smail et al., 1982). In order for adrenarche to occur, a specific cell type with the capacity to synthesize DHEA-S must arise within the adrenal glands. Cell biology experiments have shown that these cells are the zona reticularis cells of the adrenal cortex, and biochemical studies of the steroidogenic enzymes expressed in these cells explain why steroidogenesis proceeds readily to DHEA-S and no further.

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