Melanotropic Peptides: more than Just 'Barbie Drugs' and 'Sun-tan Jabs'?

E.A. Langan; Z. Nie; L.E. Rhodes

Disclosures

The British Journal of Dermatology. 2010;163(3):451-455. 

In This Article

Impact on Tanning, Sunburn and DNA Damage

Studies in the early 1990s demonstrated that subcutaneous injections of [Nle4-D-Phe7]-α-MSH increased skin pigmentation.[17] It was subsequently shown that [Nle4-D-Phe7]-α-MSH injections, given to healthy volunteers over 2 weeks, resulted in increased protective eumelanin expression in the skin, with no significant change in phaeomelanin expression.[18] These results replicated in vitro studies demonstrating an increased eumelanin/phaeomelanin ratio in cultured melanocytes exposed to [Nle4-D-Phe7]-α-MSH.[19] In humans, increased skin pigmentation occurred despite minimization of sun exposure and concomitant use of sunscreens, although it was more noticeable on sun-exposed areas, i.e. face and forearms, than covered sites.[18] A drawback of this study was that only subjects with phototypes III and IV (collectively, people who suntan easily and are more resistant to sunburn) were included, thus no conclusions could be reached about the potential increase in eumelanin in subjects with higher pheomelanin expression, i.e. phototypes I and II (collectively, people who sunburn easily and suntan with difficulty).

The intriguing possibility that [Nle4-D-Phe7]-α-MSH could have the greatest effect on increasing protective eumelanin expression in people particularly at risk of developing UVR damage was subsequently supported by a double-blind randomized placebo-controlled study published in 2006 by Barnetson et al.[20] Sixty-five subjects with low or high minimal erythemal dose (MED) were treated with three 10-day cycles of subcutaneously injected [Nle4-D-Phe7]-α-MSH over a 3-month period. It was reported that [Nle4-D-Phe7]-α-MSH preferentially increased cutaneous melanin density in subjects with the lowest baseline skin melanin levels, and also resulted in > 50% reduction in acute UVR-induced epidermal sunburn cells and 59% reduction in thymine dimer formation in the low MED group. It was therefore suggested that [Nle4-D-Phe7]-α-MSH might convey photoprotection to those most at risk of sunburn and skin cancer. Fitzgerald et al.[9] reported that [Nle4-D-Phe7]-α-MSH treatment resulted in the greatest increase in skin melanin density in individuals with MC1R variant alleles, i.e. alleles associated with fair skin and red hair. It was hypothesized that [Nle4-D-Phe7]-α-MSH might have prolonged activity in MC1R variant genotypes related to different binding points in the MC1R variants; further elucidation is awaited.

Other studies have confirmed that [Nle4-D-Phe7]-α-MSH treatment induces skin pigmentation both in the presence and absence of UVR, although UVB radiation or sunlight appears to have a synergistic effect on the tanning response.[21]

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