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Review
. 2009 Sep 15;10(9):4066-4087.
doi: 10.3390/ijms10094066.

Mechanisms regulating skin pigmentation: the rise and fall of complexion coloration

Jody P Ebanks  1   2 , R Randall Wickett  1 , Raymond E Boissy  1   2
Affiliations
Review

Mechanisms regulating skin pigmentation: the rise and fall of complexion coloration

Jody P Ebanks et al. Int J Mol Sci. .

Abstract

Skin pigmentary abnormalities are seen as aesthetically unfavorable and have led to the development of cosmetic and therapeutic treatment modalities of varying efficacy. Hence, several putative depigmenting agents aimed at modulating skin pigmentation are currently being researched or sold in commercially available products. In this review we will discuss the regulation of processes that control skin complexion coloration. This includes direct inhibition of tyrosinase and related melanogenic enzymes, regulation of melanocyte homeostasis, alteration of constitutive and facultative pigmentation and down-regulation of melanosome transfer to the keratinocytes. These various processes, in the complex mechanism of skin pigmentation, can be regulated individually or concomitantly to alter complexion coloration and thus ameliorate skin complexion diseases.

Keywords: depigmenting agents; hyperpigmentation; melanin; pigment; tyrosinase.

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Figures

Scheme 1.
Scheme 1.
Process of melanogenesis within epidermal melanosomes. Tyrosinase, the rate limiting enzyme of melanogenesis, catalyzes the hydroxylation of l-tyrosine to DOPA and the oxidation of DOPA to DOPAquinone. If cysteine or glutathione is present, it reacts with DOPAquinone to produce cysteinylDOPA and the benzothiazine derivatives of pheomelanin. As cysteine is diminished, DOPAquinone cyclizes into DOPAchrome. TYRP-2 catalyzes the tautomerization of DOPAchrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA), which is later oxidized to DHICA-melanin subunits. The oxidation of DHICA to eumelanin is thought to be catalyzed by TYRP-1. In the absence of TYRP-2 the carboxylic acid moiety of DOPAchrome is spontaneously lost to form 5,6-dihydroxyindole (DHI). DHICA in conjunction with DHI comprise subunits of eumelanin [11,12].
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