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Regulation of eumelanin/pheomelanin synthesis and visible pigmentation in melanocytes by ligands of the melanocortin 1 receptor
Author(s) -
Le Pape Elodie,
Wakamatsu Kazumasa,
Ito Shosuke,
Wolber Rainer,
Hearing Vincent J.
Publication year - 2008
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2008.00479.x
Subject(s) - melanocortin 1 receptor , melanin , tyrosinase , melanocyte , melanocortin , melanosome , chemistry , melanocyte stimulating hormone , receptor , chromatophore , pigment , microbiology and biotechnology , biochemistry , biology , enzyme , cancer research , melanoma , phenotype , genetics , gene , organic chemistry
Summary The production of melanin in the hair and skin is tightly regulated by the melanocortin 1 receptor (MC1R) whose activation is controlled by two secreted ligands, α‐melanocyte stimulating hormone (αMSH) and agouti signal protein (ASP). As melanin is extremely stable, lasting years in biological tissues, the mechanism underlying the relatively rapid decrease in visible pigmentation elicited by ASP is of obvious interest. In this study, the effects of ASP and αMSH on the regulation of melanin synthesis and on visible pigmentation were assessed in normal murine melanocytes and were compared with the quick depigmenting effect of the tyrosinase inhibitor, phenylthiourea (PTU). αMSH increased pheomelanin levels prior to increasing eumelanin content over 4 days of treatment. Conversely, ASP switched off the pigment synthesis pathway, reducing eu‐ and pheo‐melanin synthesis within 1 day of treatment that was proportional to the decrease in tyrosinase protein level and activity. These results demonstrate that the visible depigmentation of melanocytes induced by ASP does not require the degradation of existing melanin but rather is due to the dilution of existing melanin by melanocyte turnover, which emphasizes the importance of pigment distribution to visible color.