Background: Leptin is involved in the maintenance of energy balance acting on food intake, thermogenesis and energy expenditure. Via its receptor in the hypothalamus, leptin modulates the functioning of the hypothalamic-pituitary-adrenal axis and the systemic sympathetic/adrenomedullary system, which are closely linked to the regulation of energy balance and body weight. In regard of potential interactions of leptin and adrenal hormones this study intended to characterize the role of leptin in the human adrenal gland.

Materials and methods: A novel technique of laser capture microdissection was used to separate cortical and chromaffin cells for mRNA expression studies of leptin receptor isoforms and leptin mRNA in adrenal tissue and cell line NCI-H295. Immunostaining was used to localize leptin receptor in human adrenal slices. The influence of leptin on basal and ACTH-stimulated steroid hormone secretion and enzyme expression was assessed. The effect of leptin on proliferation and viability of adrenal cells in primary culture and of the NCI-H295 cell line was studied by the WST-1 assay and by 3H-thymidine test.

Results: Our data demonstrate that leptin can regulate the human adrenal function directly, via its receptors on adrenocortical cells. Leptin decreased the corticotropin-stimulated release of steroid hormones in vitro without any effect on cell proliferation. Leptin did not significantly affect the expression of cytochrome P450 scc m RNA in humans, but decreased the ACTH stimulated expression of the cytochrome P450 17alpha mRNA [corrected].

Conclusions: The adipo-adrenal interaction mediated by leptin further underscores the close link of metabolism and stress regulation in humans.