Leptin stimulates prostaglandin E-2 and F-2 alpha, but not nitric oxide production in neonatal rat hypothalamus

Leptin, an adipocyte-derived 16 kDa polypeptide hormone, has been found to regulate food intake and thermogenesis by modulating stimulatory and inhibi tory pathways in the feeding circuitry of the hypothalamus, among which cor ticotropin releasing hormone (CRH). Nitric oxide (NO) and prostaglandins ha ve been shown to be involved in both CRH neurosecretion and feeding regulat ion. We have investigated the role of NO, prostaglandin E-2 and prostagland in F-2 alpha as mediators of the hypothalamic effects of leptin and their p ossible involvement in leptin-stimulated CRH secretion. Using primary cultu res of neonatal (5- to 6-day-old) rat hypothalamic cells, we confirmed that leptin (0.1-10 nM) stimulates CRH secretion. This effect was not blocked b y L-N-G-nitro-methyl-arginine (L-NAME, 100 mu M), a NO-synthase competitive inhibitor; and leptin did not stimulate NO production. Cyclooxygenase inhi bition by indomethacin (10 mu M) did not modify leptin-induced CRH secretio n, while leptin stimulated prostaglandin E-2, and prostaglandin F-2 alpha s ecretion. In conclusion, leptin-induced hypothalamic CRH secretion is not m odulated by NO-synthase- or cyclooxygenase-mediated mechanisms; leptin does not stimulate NO production, but it stimulates prostaglandin E-2 and F-2 a lpha production, which could add to the growing list of mediators of leptin signaling in the hypothalamus. (C) 1999 Elsevier Science B.V. All rights r eserved.