VII. Topical application of a melanotropic peptide induces systemic follicular melanogenesis

We determined the relative effectiveness of α-MSH and a highly potent melanotropin analogue, [Nle⁴, D-Phe⁷]-α-MSH, in stimulating a shift from pheomelanogenesis to eumelanogenesis within hair bulbs of mice. The analogue proved to be at least a hundred times more effective than the native hormone when injected subcutaneously. The two melanotropins were then incorporated into an ointment base and topically applied to a shaved area of the skin on the back of a yellow strain of mice (C57BL/6JA^Y). Within 24-48 hours eumelanin production was visible within hair bulb melanocytes in both treated and untreated areas of animals. The presence of melanized organelles (eumelanosomes) within melanocytes was confirmed by electron microscopy. These results document the delivery of a peptide hormone through the skin and into the systematic circulation. This is the first demonstration of the delivery of a peptide hormone by percutaneous absorption and may provide a model for a similar route of delivery of other peptide hormones. The hormone analogue has also been delivered across human skin in vitro. Delivery of a melanotropin by a transdermal route may prove to be clinically useful in the treatment of some integumental hypopigmentary disorders in humans.