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Expression of Ob Receptor in Normal Human Adrenals: Differential Regulation of Adrenocortical and Adrenomedullary Function by Leptin¹

Department of Internal Medicine III, University of Leipzig, 04103 Leipzig; Medical Faculty Carl Gustav Carus TU Dresden (M.B.), Dresden; and Diabetes Research Institute, University of Duesseldorf (W.A.S.), Duesseldorf, Germany; the Department of Pathology, National Cancer Institute (J.G.), and the Developmental Endocrinology Branch, National Institute of Child Health and Human Development (G.P.C., S.R.B.) National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Dr. A. Glasow, Medizinische Klinik und Poliklinik III, University of Leipzig, Philipp-Rosenthal Strasse 27, 04103 Leipzig, Germany. E-mail: ges90apg{at}studserv.uni-leipzig.de

The major effects of leptin, an adipostatic hormone produced in fat tissue, are exerted through the hypothalamic-pituitary-adrenal axis and the systemic sympathetic/adrenomedullary system at the level of the central nervous system. 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. Functional full-length leptin receptor messenger ribonucleic acid and all human isoforms Ob219.1–3 were demonstrated by RT-PCR in both cortical and medullary tissue. Immunohistochemical staining of leptin receptor protein, however, demonstrated a strong signal only in the adrenal cortex, whereas there was weak positive staining in the medulla. Corticotropin (ACTH)-induced adrenal aldosterone, cortisol, and dehydroepiandrosterone secretion was inhibited by leptin in a concentration-dependent manner, whereas this hormone had no significant effect on catecholamine release by primary cultures of human adrenal chromaffin cells. Leptin itself was not expressed in human adrenal tissue, excluding a local paracrine or autocrine function of this peptide.

In conclusion, this is the first report identifying functional leptin receptor in human adrenal tissue and showing a differential action of leptin on human adrenocortical and chromaffin hormone production. This peripheral action of leptin on the adrenal gland provides an additional important link between the human stress response and body weight regulation.

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