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The unexpected relationship of hair color to pain tolerance appears to exist because redheads have a mutation in a hormone receptor that can apparently respond to at least two types of hormones: the pigmentation-driving melanocyte-stimulating hormone (MSH), and the pain-relieving endorphins. (Both derive from the same precursor molecule, POMC, and are structurally similar. ) Specifically, redheads have a mutated melanocortin-1 receptor (MC1R) gene that produces an altered receptor for MSH. [54] Melanocytes, the cells that produce pigment in skin and hair, use the MC1R to recognize and respond to MSH from the anterior pituitary gland. Melanocyte-stimulating hormone normally stimulates melanocytes to make black eumelanin, but if the melanocytes have a mutated receptor, they will make reddish pheomelanin instead. MC1R also occurs in the brain, where it is one of a large set of POMC-related receptors that are apparently involved not only in responding to MSH, but also in responses to endorphins and possibly other POMC-derived hormones. [54] Though the details are not clearly understood, it appears that there is some crosstalk between the POMC hormones; this may explain the link between red hair and pain tolerance.

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