Increased eumelanin expression and tanning is induced by a superpotent melanotropin [Nle(4)-D-Phe(7)]-alpha-MSH in humans

Seven normal volunteers (six males and one female) with tanning skin types III or IV (Fitzpatrick scale) were given 10 daily subcutaneous injections o f a superpotent synthetic analog of alpha-melanocyte stimulating hormone (a r-MSH) over two weeks. This agent, [Nle(4)-D-Phe(7)]alpha -MSH, also called Melanotan-I (MT-I), was administered at a dose of 0.16 mg/kg/day (Monday-F riday), over a two week period. Tanning was measured serially using compute rized light reflectance, This regimen induced tanning at 3 of 8 anatomic si tes including the face, neck and forearm by comparison of baseline to (1) t he end of the daily dosing period, (day 14), and (2) one week later, (day 2 1), Shave biopsies of the forearm taken at baseline and day 21 were analyze d by high performance liquid chromatography for eumelanin content which was measured as the permanganate oxidation product, pyrrole-2,3,5-tricarboxyli c acid or PTCA, Pheomelanin content was measured as the hydroiodic acid dig estion product, aminohydroxyphenylalanine (AHP), Eumelanin was also measure d in the forehead skin samples of three subjects, The HPLC results show tha t mean (+/- SD) baseline eumelanin (PTCA) levels in forehead skin (n = 3) a veraged 1.38 (+/-0.87) ng/mg of wet skin tissue weight. Higher mean baselin e levels of PTCA were detected in forearm skin (2.06 +/- 0.28 ng/mg wet wei ght, n = 7), One week after MT-I treatments ended, there was a mean (SD) 49 % (+/- 17.6%) increase in forehead skin PTCA levels compared to baseline (P = 0.019, n = 3, by paired sample T-test). The mean (SD) increase in forear m skin PTCA levels was 98% (+/- 25.4%) over the same period (P = 0.003), In contrast, forearm pheomelanin expression following MT-I treatment did not significantly change from baseline. Overall, the MT-I regimen increased the eumelanin: pheomelanin ratio in forearm skin from 51:1 at baseline to 86:1 following MT-I (P = 0.054 by paired sample T-test). These results show tha t the tanning induced by MT-I in the face and forearm is associated with a significant increase in the eumelanin content of the human skin.