Administration of α-MSH to C57-BL/6J mice bearing B-16 melanoma induced striking increases in tyrosinase activity and melanogenesis of the tumor. Time course studies on the increases of tyrosinase activity and melanin content of the tumor produced by one injection of α-MSH indicated that the action of α-MSH on the melanogenesis of B-16 melanoma is mediated through an increase of tyrosinase activity. Subcellular fractionation of the tumor homogenates by differential centrifugation revealed that the pattern of distribution of tyrosinase activity among the subcellular fractions remained unchanged like that of the controls, when the animals were administered 0.5 mg α-MSH per mouse per day for 2, 4, 6, 9, 12 and 21 days. This observation is considered incompatible with the hypothesis that a de novo synthesis of the enzyme took place. No tyrosinase activator was detected in the tumor from α-MSH treated mice. Therefore, it is tentatively concluded that the increase of tyrosinase activity is brought about by the removal of an inhibitor from tie tyrosinase molecules which are present in an inhibited state in the tumor. The nature of the inhibition and the mechanism through which the inhibition was removed, remain obscure at present. (Endocrinology91: 1180, 1972)
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Lee et al. (1972) studied this question.