AGOUTI PROTEIN INHIBITS THE PRODUCTION OF EUMELANIN AND PHEOMELANIN IN THE PRESENCE AND ABSENCE OF ALPHA-MELANOCYTE-STIMULATING HORMONE

Melanocytes synthesise two types of melanin: the brown-black eumelanin and the red-yellow phaeomelanin. In mice, the relative proportions of these two melanins are regulated by alpha-MSH, which preferentially i ncreases the synthesis of eumelanin and by the Agouti protein (AP), th e expression of which correlates with the growth of yellow phaeomelani n-containing hair. It has been proposed that AP acts by antagonizing t he action of alpha-MSH at the MC1 receptor, although it has been sugge sted that it may also act independently of alpha-MSH. In the present s tudy we show that AP inhibits melanogenesis in B16F1 melanoma cells in the presence and absence of alpha-MSH and also causes dose-related de creases in the synthesis of both eumelanin and phaeomelanin. In the pr esence of alpha-MSH AP had a greater effect on eumelanin production an d this is consistent with an antagonistic action at the MC1 receptor. In the absence of alpha-MSH however, AP produced similar reductions in the synthesis of both melanins. These changes were not seen in B16G4F cells which lack the MC1 receptor, suggesting that even in the absenc e of alpha-MSH AP acts at the MC1 receptor. How this action is mediate d at the intracellular level is not yet clear, although it appears to be associated with a decrease in tyrosinase activity.