Role of Nutritional Status in the Regulation of Adrenarche1

The factors regulating adrenarche are unknown. Recent in vitro studies have demonstrated that insulin and insulin-like growth factor I induce major adrenal steroidogenic enzyme genes and increase the production of adrenal androgens. Literature findings strongly suggest that changes in body mass index (BMI) reflect an integrated nonhormonal index of changes in serum levels and/or bioactivities of insulin and insulin-like growth factor I. We therefore longitudinally investigated individual changes in BMI and urinary 24-h excretion rates of dehydroepiandrosterone sulfate (DHEAS) in a prepuberty (PreC; n = 22, 11 boys and 11 girls) and a puberty (PubC; n = 20, 10 boys and 10 girls) cohort of healthy children. Twenty-four-hour urine samples were collected at yearly intervals during observation periods that lasted at least 4 yr (comprising > or = 5 consecutive 24-h urine collections). For 4-yr intervals highly significant tracking coefficients (P < 0.001) of 0.73 (PreC) and 0.93 (PubC) were observed for DHEAS, emphasizing the importance of individual (and genetic) influences on adrenal androgen excretion. In both cohorts almost 3-fold higher median increases in urinary DHEAS excretion rates (P < 0.05) were observed during the 1-yr period of the individually highest rises in BMI compared with the 1-yr period of significantly lower rises in BMI (P < 0.01) in the same children after the factor age was controlled for. However, no consistently significant associations were found between urinary DHEAS output and BMI from simple cross-sectional correlations at defined age points. These findings provide the first in vivo evidence that a change in the nutritional status, measurable in the form of delta-BMI (but not BMI alone), is an important physiological regulator of adrenarche regardless of individual adrenal androgen excretion level, age, and developmental stage.