DEXAMETHASONE RAPIDLY INCREASES HYPOTHALAMIC NEUROPEPTIDE-Y SECRETIONIN ADRENALECTOMIZED OB OB MICE/

A single intracerebroventricular injection of dexamethasone (DEX) rapi dly (within 30 min) suppresses brown adipose tissue thermogenesis and increases plasma insulin concentrations in adrenalectomized (ADX) ob/o b mice but not in ADX lean mice. Intracerebroventricular neuropeptide Y (NPY) administered intracerebroventricularly causes these same metab olic changes within 30 min in both ob/ob and lean ADX mice. We therefo re hypothesized that DEX exerts these rapid-onset metabolic actions in ob/ob mice via a phenotype-specific enhancement of NPY secretion with in the central nervous system. In support of this hypothesis, DEX (a t ype II glucocorticoid receptor agonist) administered intracerebroventr icularly selectively lowered NPY concentrations in the whole hypothala mus of ADX ob/ob mice by 35% and in the arcuate nucleus region by simi lar to 70% within 30 min but not in the brain stem or hippocampus or i n any of these regions of lean mice. DEX also functioned in vitro to e nhance depolarization-dependent release of NPY from hypothalamic block s of ADX ob/ob mice but not of ADX lean mice. Thus DEX acts in the hyp othalamus of ob/ob mice in a phenotype-specific manner to evoke rapid transport of NPY from cell bodies within the arcuate nucleus to termin al regions including the dorsomedial and ventromedial hypothalamic reg ions for release.