Premium
The molecular basis of premature adrenarche: an hypothesis
Author(s) -
Miller Walter L
Publication year - 1999
Publication title -
acta pædiatrica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 115
eISSN - 1651-2227
pISSN - 0803-5253
DOI - 10.1111/j.1651-2227.1999.tb14405.x
Subject(s) - adrenarche , endocrinology , medicine , dehydroepiandrosterone , zona reticularis , dehydroepiandrosterone sulfate , lyase , adrenal cortex , chemistry , androgen , biology , hormone , enzyme , biochemistry , zona glomerulosa , angiotensin ii , blood pressure
Adrenarche is characterized by a prepubertal rise in adrenal secretion of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) that is independent of the gonads or gonadotropins. Adrenopause is the corresponding diminution in DHEA and DHEAS concentrations in later life. The mechanisms by which adrenarche and adrenopause are induced and regulated are unknown. Early work focused on identifying hypothetical adrenal androgen regulatory hormones that would induce DHEA in much the same way that adrenocorticotropin induces cortisol, but no such factors have been found. Current studies of adrenarche focus on intra‐adrenal events, particularly those concerning 3β‐hydroxysteroid dehydrogenase (3β‐HSD) and 17α‐hydroxylase/17,20‐lyase (P450c17). Molecular data implicate a decrease in 3β‐HSD specifically in the adrenal zona reticularis. However, a decrease in 3β‐HSD is insufficient to explain why the reticularis catalyzes 17,20‐lyase activity and hence makes DHEA, rather than catalyzing only 17α‐hydroxylase activity, as does the zona fasciculata. P450c17 appears to catalyze 17,20‐lyase activity only if P450c17 has undergone serine phosphorylation and has access to cytochrome b 5 as an allosteric cofactor. Although these two factors have not yet been investigated in adrenarche, it appears that both a zone‐specific diminution in 3β‐HSD and a zone‐specific induction of 17,20‐lyase activity are required to account for the physiological data. Exaggerated premature adrenarche appears to be an early sign of polycystic ovary syndrome (PCOS). Mechanistic considerations of PCOS suggest a key role for serine phosphorylation of P450c17 in both adrenarche and some forms of heritable PCOS.