Prolonged Administration of Leptin Inhibits Proliferation and Stimulates Apoptosis in the Rat Adrenal Gland

Leptin, the product of the ob gene, is an adipose tissue-secreted hormone, which acts to decrease caloric intake and to increase energy expenditure. Some of the leptin effects on energy balance are known to be mediated by the hypothalamo-pituitary-adrenal axis. Chronic leptin administration has been found to inhibit pituitary ACTH release and to cause adrenal atrophy in the rat. However, the mechanisms involved in this last effect of leptin are not yet settled. Adult female rats received daily subcutaneous injections of leptin[1-147] and its fragment 116-130 at a dose of 20 nmol/kg day for 6 consecutive day, and the effect on the proliferative activity and apoptotic rate of adrenocortical cells were studied by the proliferating-cell nuclear antigen (PCNA)-immunostaining and in situ TUNEL assay technique, respectively. Leptin chronic administration lowered adrenal weight and decreased PCNA-index in the zona glomerulosa, leptin[116-130] being more effective than leptin[1-147]. Both leptins raised apoptotic-index in the zona fasciculata and to a lesser extent in the zona reticularis. Collectively, the present findings indicate that chronic leptin treatment inhibits proliferation and enhances apoptosis in the rat adrenal cortex, these effects being responsible for the adrenal atrophy and possibly consequent to the leptin-induced inhibition of pituitary ACTH release.