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Variants of the Melanocyte-Stimulating Hormone-Receptor Gene Are Associated with Red Hair and Fair Skin in Humans

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Paloma Valverde at Paloma Valverde Consulting, LLC
Paloma Valverde
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Eugene Healy
Eugene Healy
Eugene Healy
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Ian J. Jackson at University of Edinburgh
Ian J. Jackson
Jonathan L Rees at University of Edinburgh
Jonathan L Rees
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Abstract

Melanin pigmentation protects the skin from the damaging effects of ultraviolet radiation (UVR). There are two types of melanin, the red phaeomelanin and the black eumelanin, both of which are present in human skin. Eumelanin is photoprotective whereas phaeomelanin, because of its potential to generate free radicals in response to UVR, may contribute to UV-induced skin damage. Individuals with red hair have a predominance of phaeomelain in hair and skin and/or a reduced ability to produce eumelanin, which may explain why they fail to tan and are at risk from UVR. In mammals the relative proportions of phaeomelanin and eumelanin are regulated by melanocyte stimulating hormone (MSH), which acts via its receptor (MC1R), on melanocytes, to increase the synthesis of eumelanin and the product of the agouti locus which antagonises this action. In mice, mutations at either the MC1R gene or agouti affect the pattern of melanogenesis resulting in changes in coat colour. We now report the presence of MC1R gene sequence variants in humans. These were found in over 80% of individuals with red hair and/or fair skin that tans poorly but in fewer than 20% of individuals with brown or black hair and in less than 4% of those who showed a good tanning response. Our findings suggest that in humans, as in other mammals, the MC1R is a control point in the regulation of pigmentation phenotype and, more importantly, that variations in this protein are associated with a poor tanning response.
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© 1995 Nature Publishing Group http://www.nature.com/naturegenetics
© 1995 Nature Publishing Group http://www.nature.com/naturegenetics
© 1995 Nature Publishing Group http://www.nature.com/naturegenetics
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... The MC1R gene is among the most extensively studied genes in relation to pigmentation. Variations within this gene have been shown to correlate with lighter skin and hair colors, particularly in European populations [5]. ...
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Article
  • Aug 1995
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Mountjoy, K.G., Robbins, L.S., Mortrud, M.T. & Cone, R.D. The cloning of a family of genes that encode the melanocortin receptors. Science 257, 1248-1251
Article
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Melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) regulate pigmentation and adrenal cortical function, respectively. These peptides also have a variety of biological activities in other areas, including the brain, the pituitary, and the immune system. A complete understanding of the biological activities of these hormones requires the isolation and characterization of their corresponding receptors. The murine and human MSH receptors (MSH-Rs) and a human ACTH receptor (ACTH-R) were cloned. These receptors define a subfamily of receptors coupled to guanine nucleotide-binding proteins that may include the cannabinoid receptor.
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Pheomelanin as well as Eumelanin Is Present in Human Epidermis
Article
  • Sep 1991
There are two types of melanin in mammals, the brownish black eumelanin and the reddish yellow pheomelanin. Eumelanin and pheomelanin are present in human hair and this study was carried out to see whether both pigments are also present in human epidermis. Samples of epidermis were obtained from suction blisters raised in the upper arm of 13 Caucasian subjects of skin types I, II, and III and analyzed for both eumelanin and pheomelanin using a procedure involving high-performance liquid chromatography. Eumelanin and pheomelanin were found in all epidermal samples and their relative proportions correlated well with those found in samples of hair taken from the same subjects. The lowest concentrations of eumelanin were found in subjects of skin type I, with higher levels in skin types II and III. The concentrations of pheomelanin were more variable and showed no relationship to skin type. Increases in the concentrations of both pigments occurred following PUVA therapy, but whereas the largest increases in eumelanin were seen in skin types II and III, the increases in pheomelanin showed little relationship to skin type. Unlike eumelanin, epidermal pheomelanin also showed little relationship to PUVA-induced tanning. The present findings could be particularly significant in view of recent suggestions that pheomelanin, rather than protecting the skin against UV radiation, may actually contribute to UV-induced skin damage.
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Effects of Melanin-Induced Free Radicals on the Isolated Rat Peritoneal Mast Cells
Article
  • Apr 1986
Pheomelanin from human red hair (RHM) produces considerably more cellular damage in Ehrlich ascites carcinoma cells when subjected to radiations of wavelength 320-700 nm than eumelanin from black hair (BHM). Irradiation of RHM generated large amounts of superoxide while BHM did not produce detectable amounts of superoxide. The present investigations describe the effects of irradiation of mast cells in the presence of various natural and synthetic melanins. Irradiation of mast cells in the presence of RHM and red hair melanoprotein released large amounts of histamine while BHM and synthetic melanins prepared from dopa, cysteinyldopa, or a mixture of dopa and cysteinyldopa did not release histamine. The release of histamine at lower concentrations of RHM was not accompanied by the release of 51Cr from chromium-loaded cells, suggesting that this release was of noncytotoxic nature. On the other hand, the release of histamine at higher concentrations of RHM was due to cell lysis since both histamine and cytoplasmic marker 51Cr were released to the same extent. The release evoked by large concentration RHM was not inhibited by superoxide dismutase or catalase. This suggests that the cell lysis under these conditions was not due to H2O2 or O-2. The finding that mast cells release histamine when irradiated in the presence of RHM suggests that the immediate and late-phase reactions seen in sunburn may in part be due to the release of mediators from these cells.
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