Expression of Ob receptor in normal human adrenals: Differential regulation of adrenocortical and adrenomedullary function by leptin

The major effects of leptin, an adipostatic hormone produced in fat tissue, are exerted through the hypothalamic-pituitary-adrenal axis and the system ic sympathetic/adrenomedullary system at the level of the central nervous s ystem. Here, we examined the direct effects of leptin on the adrenal gland, a peripheral end organ of both the hypothalamic-pituitary-adrenal axis and the sympathetic/adrenomedullary system. As cortical and chromaffin tissues are intermingled in the human adrenal, we employed the novel technique of laser capture microdissection to analyze these systems separately. Function al full-length leptin receptor messenger ribonucleic acid and all human iso forms Ob219.1-3 were demonstrated by RT-PCR in both cortical and medullary tissue. Immunohistochemical staining of leptin receptor protein, however, d emonstrated a strong signal only in the adrenal cortex, whereas there was w eak positive staining in the medulla. Corticotropin (ACTH)-induced adrenal aldosterone, cortisol, and dehydroepiandrosterone secretion was inhibited b y leptin in a concentration-dependent manner, whereas this hormone had no s ignificant effect on catecholamine release by primary cultures of human adr enal chromaffin cells. Leptin itself was not expressed in human adrenal tis sue, excluding a local paracrine or autocrine function of this peptide. In conclusion, this is the first report identifying functional leptin recep tor in human adrenal tissue and showing a differential action of leptin on human adrenocortical and chromaffin hormone production. This peripheral act ion of leptin on the adrenal gland provides an additional important link be tween the human stress response and body weight regulation.