期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 660, 期 1, 页码 103-110出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2010.11.040
关键词
MC1R; Melanoma; Red hair colour; Melanocyte; Tanning; Pigmentation
资金
- National Health and Medical Research Council of Australia [NHMRC-511191, NHMRC-552485]
- Australian Research Council [ARC-DP0771169]
- National Institutes of Health [NIH-R01DK064265]
- NHMRC [NHMRC-511029]
The melanocortin MC1 receptor is a G-protein coupled receptor expressed in the melanocytes of the skin and hair and is known for its key role in the regulation of human pigmentation. Melanocortin MC1 receptor activation after ultraviolet radiation exposure results in a switch from the red/yellow pheomelanin to the brown/black eumelanin pigment synthesis within cutaneous melanocytes; this pigment is then transferred to the surrounding keratinocytes of the skin. The increase in melanin maturation and uptake results in tanning of the skin, providing a physical protection of skin cells from ultraviolet radiation induced DNA damage. Melanocortin MC1 receptor polymorphism is widespread within the Caucasian population and some variant alleles are associated with red hair colour, fair skin, poor tanning and increased risk of skin cancer. Here we will discuss the use of mouse coat colour models, human genetic association studies, and in vitro cell culture studies to determine the complex functions of the melanocortin MC1 receptor and the molecular mechanisms underlying the association between melanocortin MC1 receptor variant alleles and the red hair colour phenotype. Recent research indicates that melanocortin MC1 receptor has many non-pigmentary functions, and that the increased risk of skin cancer conferred by melanocortin MC1 receptor variant alleles is to some extent independent of pigmentation phenotypes. The use of new transgenic mouse models, the study of novel melanocortin MC1 receptor response genes and the use of more advanced human skin models such as 3D skin reconstruction may provide key elements in understanding the pharmacogenetics of human melanocortin MC1 receptor polymorphism. (C) 2010 Elsevier B.V. All rights reserved.
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