Chapter 2 55 appears to be very important during each individual’s lifespan. In contrast to the continuous melanogenesis observed in epidermal melanocytes, follicular melanogenesis is a strictly anagen-coupled, cyclic phenomenon. It is shut off early during the anagen–catagen transition, beginning with the down-regulation of key enzymes of melanogenesis and followed by the apoptosis of hair follicle melanocyte.64 In mammals, melanin pigments are derivatives of the amino acid tyrosine as shown in Figure 6. Two common forms of biological melanin are eumelanin, a brown-black polymer of dihydroxyindole carboxylic acids, and pheomelanin, a red-brown polymer of benzothiazine units largely responsible for red hair and freckles. The essential and rate-limiting enzyme in the melanin biosynthetic pathway is tyrosinase, which is a multifunctional, glycosylated, copper-containing oxidase with a molecular weight of approximately 60–70 kDa. Tyrosinase is synthesized in melanosomal ribosomes found on the rough endoplasmic reticulum and catalyzes the initial events of melanogenesis. Eumelanin and pheomelanin are biologically related and arise from the same key intermediate, dopaquinone. A mixture of eumelanin and pheomelanin generated by melanocytes will confer mature hair and skin different colors. By ultrastructure and biochemical analysis, it has been demonstrated that human hair, regardless of its color, contains various combinations of eumelanin and pheomelanin. These discoveries suggest the existence of the molecular mechanisms that direct the switch between the synthesis of eumelanin and pheomelanin by follicular melanocytes. The product protein from murine agouti gene influences whether eumelanin, pheomelanin, or both are synthesized in differentiated follicular melanocytes. There are various mutations in agouti gene in the mice conferring different hair coat color, from yellow to black. It was later discovered that agouti product actually competes with α-melanocyte stimulating hormone (α-MSH) to bind with the melanocortin 1 receptor (MC1R), also known as the melanocyte-stimulating hormone receptor. MC1R is one of the key proteins involved in regulating