title: New ligands for melanocortin receptors.
abstract: Named originally for their effects on peripheral end organs, the melanocortin system controls a diverse set of physiological processes through a series of five G-protein-coupled receptors and several sets of small peptide ligands. The central melanocortin system plays an essential role in homeostatic regulation of body weight, in which two alternative ligands, alpha-melanocyte-stimulating hormone and agouti-related protein, stimulate and inhibit receptor signaling in several key brain regions that ultimately affect food intake and energy expenditure. Much of what we know about the relationship between central melanocortin signaling and body weight regulation stems from genetic studies. Comparative genomic studies indicate that melanocortin receptors used for controlling pigmentation and body weight regulation existed more than 500 million years ago in primitive vertebrates, but that fine-grained control of melanocortin receptors through neuropeptides and endogenous antagonists developed more recently. Recent studies based on dog coat-color genetics revealed a new class of melanocortin ligands, the beta-defensins, which reveal the potential for cross talk between the melanocortin and the immune systems.
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: C B
authors.initials: CB
authors.lastname: Kaelin
authors.forename: S I
authors.initials: SI
authors.lastname: Candille
authors.forename: B
authors.initials: B
authors.lastname: Yu
authors.forename: P
authors.initials: P
authors.lastname: Jackson
authors.forename: D A
authors.initials: DA
authors.lastname: Thompson
authors.forename: M A
authors.initials: MA
authors.lastname: Nix
authors.forename: J
authors.initials: J
authors.lastname: Binkley
authors.forename: G L
authors.initials: GL
authors.lastname: Millhauser
authors.forename: G S
authors.initials: GS
authors.lastname: Barsh
mesh_terms: D054366:Agouti Signaling Protein; D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology*; D002490:Central Nervous System / Q000378:metabolism / Q000502:physiology*; D004285:Dogs; D004435:Eating / Q000235:genetics / Q000502:physiology*; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006801:Humans; D008024:Ligands; D053486:Melanocortins / Q000378:metabolism; D010858:Pigmentation / Q000235:genetics; D044101:Receptors, Melanocortin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000521:alpha-MSH / Q000378:metabolism; D023083:beta-Defensins / Q000502:physiology
chemical_list: D054366:Agouti Signaling Protein; D054369:Agouti-Related Protein; D008024:Ligands; D053486:Melanocortins; D044101:Receptors, Melanocortin; D023083:beta-Defensins; D000521:alpha-MSH