Melanocortin signalling mechanisms.

The melanocortin family are a series of very potent neuropeptides that derive from a parent propopiomelanocortin molecule (POMC). They are expressed predominantly in the brain, specifically the pituitary gland and also in the central nervous system. Interestingly, recent research also suggests the existence of regulatory functions outside of the brain, in a wide range of peripheral tissues. Several important melanocortin peptides with differing functions are created by the tissue-specific proteolytic cleavage of POMC, generating peptides including ACTH and α-MSH. For many years the major recognised function of α-MSH was an ability to stimulate melanocyte cells of the skin to pigment. However, a number of parallel functions unrelated to melanogenesis have been described in the literature for several years. A more complete understanding of this work arose after the discovery and cloning of the melanocortin receptors in 1992, which lead to the recognition of many wider roles of the melanocortin peptides. The knowledge of the tissue in which a given receptor subtype was expressed could now be combined with functional downstream studies. From these studies, we know that α-MSH has a very significant role in controlling inflammation and immunomodulation, with other roles including control over energy homeostasis and exocrine secretion, an ability to trigger erectile functions and the control of sexual behaviour. This chapter will briefly review the melanocortin system and melanocortin receptors, with a focus on the key signalling mechanisms of α-MSH and how these link receptors through to function.