Article

Melanocortin Receptor Ligands: New Horizons for Skin Biology and Clinical Dermatology

Department of Dermatology and Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, University of Münster, Germany.
Journal of Investigative Dermatology (Impact Factor: 6.37). 08/2006; 126(9):1966-1975. DOI: 10.1038/sj.jid.5700421

ABSTRACT The melanocortin (MC) system is probably the best characterized neuropeptide network of the skin. Most cutaneous cell types express MC receptors (MC-Rs) and synthesize MCs, such as -melanocyte-stimulating hormone (-MSH), that act in autocrine and paracrine fashion. In human skin cells, activation of adenylate cyclase by MCs occurs at 10-6–10-9 M doses of the ligand, but effects are induced in some cell types at subnanomolar concentrations. In addition to the pigmentary action of MCs on epidermal melanocytes, the hair follicle is a source and target for MCs. MCs regulate lipogenesis in sebocytes expressing both MC-1R and MC-5R. In adipocytes, lipid metabolism is modulated by agouti signalling protein, a natural MC-1R/MC-4R antagonist. The anti-inflammatory activity of -MSH includes immunomodulatory effects on several resident skin cells and antifibrogenic effects mediated via MC-1R expressed by dermal fibroblasts. In human mast cells, -MSH appears to be proinflammatory due to histamine release. -MSH exhibits cytoprotective activity against UVB-induced apoptosis and DNA damage, a finding that helps explain the increased risk of cutaneous melanoma in individuals with loss of function MC-1R mutations. These findings should improve our understanding of skin physiology and pathophysiology and may offer novel strategies with MCs as future therapeutics for skin diseases.Abbreviations: AGRP, agouti-related peptide; AP, agouti protein; ASP, Agouti signalling protein; GRK, G protein-coupled receptor kinase; LPS, lipopolysaccharide; MC, melanocortin; Mc-r, (murine) melanocortin receptor; MC-R, (human) melanocortin receptor; MSH, melanocyte-stimulating hormone; POMC, proopiomelanocortin; RHC, red hair and fair skin; TGF-, transforming growth factor-; TM, transmembrane; TNF-, tumor necrosis factor-

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