AGOUTI PROTEIN CAN ACT INDEPENDENTLY OF MELANOCYTE-STIMULATING HORMONE TO INHIBIT MELANOGENESIS

In animals, the coat-darkening effects of alpha-melanocyte stimulating hormone (alpha-MSH) are opposed by agouti protein. Although agouti pr otein has been shown to be a competitive antagonist of the melanocyte- associated MC-1 melanocortin receptor, the possibility that agouti pro tein can affect melanogenesis independently of its ability to antagoni se melanocortin activity cannot be excluded. This study demonstrates t hat murine agouti protein causes both a time- and concentration-depend ent suppression of melanogenesis in B16 F1 murine melanoma cells. In a ddition, human agouti protein decreases melanogenesis in cultured huma n epidermal melanocytes. However, agouti protein has little effect on the ability of alpha-MSH to stimulate melanogenesis. These observation s raise fundamental questions about the mode of action of agouti prote in in regulating melanogenesis.