LEPTIN RECEPTORS IN THE ADRENAL-MEDULLA OF THE RAT

Leptin is the protein product of the recently cloned obesity gene. Lep tin receptor mRNA is found in a number of central and peripheral locat ions. The hypothalamus is a presumed site of action. However, little i s known about the specific locations of the receptor in peripheral org ans. Epinephrine has potent anorectic effects and can cause weight los s by a variety of mechanisms. Excretion of epinephrine is reduced in t he ob/ob mouse, which lacks leptin, suggesting an effect by leptin on the adrenal medulla. In the current study, the presence of the leptin receptor was identified on epinephrine-secreting cells in the adrenal medulla. Immunohistochemical studies found dense leptin receptor-like immunoreactivity in the adrenal medulla with no labeling in the adrena l cortex. Double immunofluorescent labeling confirmed that the leptin receptor was present on cells that were phenylethanolamine N-methyltra nsferase-like immunoreactive and therefore were epinephrine-secreting cells. Leptin receptor mRNA in the adrenal medulla was detected by rev erse transcriptase-polymerase chain reaction, with the majority of the mRNA coding for the short isoform (Ob-Ra) of the receptor. Finally au toradiography was performed using I-125-labeled leptin; specific bindi ng was found in the adrenal medulla, with no specific binding in the a drenal cortex. These results suggest that leptin may have a direct eff ect on epinephrine-secreting cells in the adrenal medulla. Epinephrine may play a role in mediating the effects of leptin to reduce body wei ght.