Non-pigmentary actions of alpha-melanocyte-stimulating hormone--lessons from the cutaneous melanocortin system

In the last years the neuropeptide a-melanocyte-stimulating hormone has emerged as a regulator of various biological processes far beyond the initially described pigment-inducing action. Expression of melanocortin-receptors (MC-Rs), mainly MC-1R, has been identified in several non-pigmentary human skin cell types. Moreover, expression of MC-5R has been detected in sebocytes and skin mast cells while MC-4R has been reported in dermal papilla cells, a specialized myofibroblast cell type regulating hair follicle activity. In accordance with early observations in the rat preputial gland alpha-melanocyte-stimulating and related peptides have lipogenic activity in the human system. The immunomodulatory actions of alpha-melanocyte-stimulating include regulation of expression and secretion of chemokines, downregulation of proinflammatory signal-induced NF-kappaB activation and adhesion molecule expression, prostaglandin E2 synthesis, as well as induction of interleukin-10. Depending on the cell type studied and the experimental conditions alpha-melanocyte-stimulating however may also have weak proinflammatory actions. In dermal fibroblasts alpha-melanocyte-stimulating was further reported to modulate collagen metabolism via upregulating interstitial collagenase as well as by attenuating the inductive effect of transforming growth factor B on 1 collagen synthesis and fibrosis, the latter pointing towards a potential role of a-melanocyte-stimulating during chronic inflammatory skin responses. The immunomudulatory effects, the established melanotropic action and the recently identified cytoprotective activity of a-melanocyte-stimulating on UVB-induced apoptosis and DNA damage may be part of the body's host defence in which this neuropeptide--typically induced by proinflammatory signals--maintains tissue homeostasis and prevents genotoxicity during inflammatory responses.