GLUCOCORTICOID REGULATION OF LEPTIN SYNTHESIS AND SECRETION IN HUMANS- ELEVATED PLASMA LEPTIN LEVELS IN CUSHINGS-SYNDROME

Leptin, the obese (ob) gene product, is an adipocyte-derived satiety f actor that is involved in the regulation of food ingestion and body we ight. To investigate glucocorticoid regulation of leptin synthesis and secretion in humans, we measured plasma leptin levels in patients wit h Gushing's syndrome with adrenal or pituitary adenoma and in patients with iatrogenic Gushing's syndrome. Plasma leptin levels in patients with Gushing's syndrome were significantly elevated compared to those in nonobese healthy subjects and obese subjects without any metabolic or endocrine diseases at a given percentage of body fat by analysis of covariance. In patients with adrenal or pituitary adenoma, after the tumor resection, plasma leptin levels were reduced, with a concurrent decrease in plasma cortisol levels. With no significant changes in bod y weight, plasma leptin levels were also elevated significantly in lea n healthy volunteers 24 h after the admistration of 1 mg dexamethasone . Dexamethasone potently induced ob gene expression and leptin secreti on in the organ culture of human adipose tissue. The data demonstrate that glucocorticoids act, at least in part, directly on the adipose ti ssue and increase leptin synthesis and secretion in humans.