Leptin prolonged administration inhibits the growth and glucocorticoid secretion of rat adrenal cortex

Leptin is an adipose-tissue secreted hormone, that acts to decrease caloric intake and to increase energy expenditure. Some of the leptin effects on the energy balance are known to be mediated by the hypothalamo-pituitary-adrenal (HPA) axis, but the role of this cytokine in the regulation of the growth and steroidogenic capacity of adrenal cortex is still controversial. Therefore, the present study was designed to explore the long-term effects of native leptin[1-147] and its biologically active fragment leptin[116-130] (6 daily subcutaneous injection of 20 nmol/kg) on the rat HPA axis. Leptin[1-147] and leptin[116-130] caused a significant adrenal atrophy, which was mainly due to the decrease in the volume of zona fasciculata (ZF) and in the number of its parenchymal cells. Both leptins provoked a marked drop in the plasma concentrations of ACTH and corticosterone, the main hormone produced by ZF cells. The effects of leptin[116-130] were more intense than those of leptin[1-147]. Leptin[1-147], but not its fragment, evoked a clear-cut rise in the plasma concentration of aldosterone. Collectively, these findings indicate that prolonged leptin administration, by inhibiting pituitary ACTH release, exerts a potent suppressive action on the growth and glucocorticoid secretory capacity of the adrenal cortex in the rat. The mechanism(s) underlying the aldosterone secretagogue action of native leptin remain(s) to be investigated.