Melanocortin Receptors and Antagonists Regulate Pigmentation and Body Weight

Bioessays. 1998 Aug;20(8):603-6. doi: 10.1002/(SICI)1521-1878(199808)20:8<603::AID-BIES1>3.0.CO;2-J.


The action 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, alpha-melanocyte-stimulating hormone (alpha-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 alpha-MSH and antagonized by agouti, both of which contribute to the variability seen in mammalian coat color.

Publication types

  • Review

MeSH terms

  • Agouti Signaling Protein
  • Animals
  • Body Weight*
  • Hair Color / genetics*
  • Hair Color / physiology
  • Intercellular Signaling Peptides and Proteins*
  • Mammals
  • Mice
  • Mice, Mutant Strains
  • Proteins / physiology*
  • Receptors, Corticotropin / antagonists & inhibitors
  • Receptors, Corticotropin / physiology*
  • Receptors, Melanocortin
  • alpha-MSH / antagonists & inhibitors
  • alpha-MSH / physiology


  • Agouti Signaling Protein
  • Intercellular Signaling Peptides and Proteins
  • Proteins
  • Receptors, Corticotropin
  • Receptors, Melanocortin
  • a protein, mouse
  • alpha-MSH