Melanocortin receptors and antagonists regulate pigmentation and body weight

The action of two genetic loci—agouti and the melanocortin receptor‐1 (Mc1r)—have opposing effects in the control of mammalian pigmentation and ultimately determine the color of the pigment produced. In a recent paper, Ollmann et al. confirmed that the agouti protein acts via the Mc1r. They show that high‐affinity binding of the agouti protein to Mc1r expressed in mammalian cells can be inhibited by the receptor's natural ligand, α‐melanocyte‐stimulating hormone (α‐MSH). In addition, genetic studies using mice carrying mutations at the Mc1r and agouti loci on a sensitized background of low tyrosinase expression confirm that a functional Mc1r is required for the maximum pigmentary effect of agouti. Thus, the Mc1r appears to be a unique, bifunctionally controlled receptor, activated by α‐MSH and antagonized by agouti, both of which contribute to the variability seen in mammalian coat color. BioEssays 20:603–606, 1998. © 1998 John Wiley & Sons Inc.