Leptin stimulates prostaglandin E2 and F2alpha, 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 inhibitory pathways in the feeding circuitry of the hypothalamus, among which corticotropin releasing hormone (CRH). Nitric oxide (NO) and prostaglandins have been shown to be involved in both CRH neurosecretion and feeding regulation. We have investigated the role of NO, prostaglandin E2 and prostaglandin F2alpha as mediators of the hypothalamic effects of leptin and their possible involvement in leptin-stimulated CRH secretion. Using primary cultures 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 by L-N(G)-nitro-methyl-arginine (L-NAME, 100 microM), a NO-synthase competitive inhibitor; and leptin did not stimulate NO production. Cyclooxygenase inhibition by indomethacin (10 microM) did not modify leptin-induced CRH secretion, while leptin stimulated prostaglandin E2, and prostaglandin F2alpha secretion. In conclusion, leptin-induced hypothalamic CRH secretion is not modulated by NO-synthase- or cyclooxygenase-mediated mechanisms; leptin does not stimulate NO production, but it stimulates prostaglandin E2 and F2alpha production, which could add to the growing list of mediators of leptin signaling in the hypothalamus.
Brunetti
L
L
Institute of Scienza del Farmaco, G. D'Annunzio University, School of Pharmacy, Chieti, Italy.
Orlando
G
G
Michelotto
B
B
Ragazzoni
E
E
Vacca
M
M
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000096:biosynthesis / Q000502:physiology*; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D020738:Leptin; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D051381:Rats
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D020738:Leptin; D011506:Proteins; D009569:Nitric Oxide; D003346:Corticotropin-Releasing Hormone; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin