Melanocortins and their implication in melanoma.

The melanocortins (MCs), that is, the melanocyte-stimulating hormones (MSHs) and ACTH, are a group of related peptides containing the typical melanotropin core sequence, His-Phe-Arg-Trp, and are derived from a common precursor, pro-opiomelanocortin. They are pleiotropic molecules that occur in the pituitary, some brain regions, and also in several peripheral tissues, and they exert a variety of physiologic functions. Their effect on melanogenesis in the skin is well established, but their role in melanocyte and melanoma cell proliferation and metastasis is less clear. The recent cloning of five types of MC receptors (MC1-5), new studies on the regulation of these receptors, the discovery of a naturally occurring MSH antagonist, the agouti protein, and the finding that melanocytes and melanoma cells exclusively express MC1 receptors have laid the basis for the future development of specific MC ligands, which may become useful for melanoma diagnosis and eventually therapy.