Leptin rapidly inhibits hypothalamic neuropeptide Y secretion and stimulates corticotropin-releasing hormone secretion in adrenalectomized mice

Leptin may rapidly inhibit food intake by altering the secretion of hypotha lamic neuropeptides such as neuropeptide Y (NPY), a stimulator of food inta ke, and/or corticotropin-releasing hormone (CRH), an inhibitor of food inta ke, We measured concentrations of NPY and CRH in specific hypothalamic regi ons [i.e., arcuate nucleus (ARC), paraventricular nucleus (PVN), ventromedi al nucleus and dorsomedial nucleus] of 7- to 8-wk-old lean and ob/ob mice a t 1 or 3 h after intracerebroventricular leptin administration. No rapid-on set effects of leptin on hypothalamic NPY or CRH concentrations were observ ed in intact mice. The addition of leptin to hypothalamic preparations from intact mice also did not alter NPY or CRH secretion. Glucocorticoids may o ppose leptin actions. Consistent with this, leptin administration to adrena lectomized mice markedly reduced CRH concentrations in the ARC within 3 h a fter injection. This rapid reduction in CRH concentration in the ARC after leptin administration is more likely due to stimulated CRH release from thi s region than to decreased synthesis/transport from the PVN because leptin stimulates CRH synthesis in the PVN, Within 20 min after exposure to leptin , NPY secretion from hypothalamic preparations obtained from adrenalectomiz ed mice was lowered by 27% and CRH secretion was elevated by 51%, The curre nt study demonstrates that leptin rapidly influences the secretion of hypot halamic NPY and CRH and that these actions of leptin within the hypothalamu s are restrained by the presence of endogenous corticosterone.