Skill POMC peptides: Their actions at the human MC-1 receptor and roles inthe tanning response

The melanocortin 1 (MC-1) receptor is a key control point in the regulation of skin pigmentation, alpha-MSH is an agonist at tills receptor and throug h its activation regulates melanocyte function. alpha-MSH is cleared from p ro-opiomelanocortin (POMC) in the pituitary, but in humans the skin is a mo re important source of the peptide. Skin pigmentation is therefore regulate d by locally produced alpha-MSH rather than that of pituitary origin. alpha -MSH acts as a paracrine and/or autocrine mediator of UV induced pigmentati on. However, the predominant alpha-MSH in human skin is desacetyl alpha-MSH and, compared to the acetylated form, is a relatively weak agonist at the human MC-1 receptor. By acting as a partial agonist desacetyl alpha-MSH may even oppose the actions of acetylated alpha-MSH and other MC-1 receptor ag onists, The most abundant MC-1 receptor agonist in human epidermis is ACTH1 -17, This POMC peptide, which is produced by keratinocytes, is more potent than acetylated alpha-MSH in stimulating melanogenesis in human melanocytes and, in contrast to the latter, produces a biphasic dose-response curve. T his is probably a consequence of its activation of both the cAMP and IP3/DA G signalling pathways, alpha-MSH peptides, on the other hand, selectively a ctivate the cAMP pathway, Compared with alpha-MSH, ACTH1-17 could have the more important role as a paracrine mediator of melanogenesis and other mela nocytic processes. However, ACTH1-17 is not the only POMC peptide in the sk in and may interact with related peptides at the MC-1 receptor. These inter actions are likely to represent important determinants of melanocyte functi on and skin pigmentation.