Direct Inhibitory Effects of Leptin on the Neonatal Adrenal and Potential Consequences for Brain Glucocorticoid Feedback

Abstract

Leptin is most studied for its primary role in the CNS control of energy balance and food intake in humans and rodents, yet it has functions on multiple target sites including the adrenal gland. In adult rodents, leptin has been shown to inhibit adrenal steroidogenesis and we have recently demonstrated that some of the mechanisms responsible for leptin-induced inhibition of adrenal glucocorticoid production, namely a reduction of StAR protein expression are already present in the neonatal adrenal gland. The effect of leptin on the neonatal adrenal gland integrates well with the previously demonstrated effect of this protein to inhibit stress responses, enhance glucocorticoid receptor expression in the CNS and sensitivity to glucocorticoid inhibitory feedback in neonates. The leptin receptor isoform and intracellular mechanisms involved in regulation of the adrenocortical activity at multiple levels might differ between target tissues (CNS vs periphery) and age (neonates vs adult). Neonatal leptin represents an important regulator of adrenocortical function during a critical period of brain development, which is exquisitely sensitive to circulating glucocortcoid concentrations. Since circulating leptin levels in neonates vary according to maternal diet, this protein can be viewed as a critical link between environmental and maternal factors and the developing physiology of the infant.