In the human skin, melanocytes are present in the epidermis and hair follicles. The basic features of these cells are the ability to melanin production and the origin from neural crest cells. This last element is important because there are other cells able to produce melanin but of different embryonic origin (pigmented epithelium of retina, some neurons, adipocytes). The life cycle of melanocyte consists of several steps including differentiation of melanocyte lineage/s from neural crest, migration and proliferation of melanoblasts, differentiation of melanoblasts into melanocytes, proliferation and maturation of melanocytes at the target places (activity of melanogenic enzymes, melanosome formation and transport to keratinocytes) and eventual cell death (hair melanocytes). Melanocytes of the epidermis and hair are cells sharing some common features but in general they form biologically different populations living in unique niches of the skin.

Melanogenesis is a biochemical pathway responsible for melanin synthesis [37]. It takes place in melanocytes, in separate cytoplasmic organelles called melanosomes [11]. Two major types of melanin are produced – pheomelanin and eumelanin. They differ in color and the way of synthesis. Melanin has numerous properties which are beneficial to the body: UV light absorption and scattering, free radical scavenging, coupled oxidation-reduction reactions and ion storage [23, 38, 39]. The availability of substrates and the function of melanogenesis enzymes decide about the types of melanins produced (Figure 4). Tyrosinase (TYR) carries out tyrosine hydroxylation to L-3,4-dihydroxyphenylalanine (DOPA) which is rapidly oxidized to DOPAquinone [40]. In the presence of cysteine DOPAquinone react with it, yielding 3- or 5-cysteinylDOPAs, which then oxidize and polymerize, giving rise to yellow-red soluble melanin – pheomelanin [37, 41]. In the absence of thiols (cysteine, glutathione or thioredoxin) brown-black eumelanin is produced. DOPAquinone spontaneously undergoes cyclization to DOPAchrome [42]. The DOPAchrome spontaneously loses carboxylic acid and generates 5,6-dihydroxyindole (DHI), which rapidly oxidizes and polymerizes to form dark brown-black, insoluble DHI-melanin. However, if DOPAchrome tautomerase (TYRP2/DCT) is present, DOPAchrome will form DHI-2-carboxylic acid (DHICA) [43]. Tyrosinase and TYRP1 catalyze further conversions obtaining finally a lighter brown color DHICA-melanin [30, 37]. Human skin contains a mixture of all melanin types, and the ratio of those in part determines visible pigmentation [19]. Diversity of skin pigmentation among different ethnic groups is preserved and depends on eumelanin content. The ratio of eumelanin to total melanin decide about skin color [30]. Pheomelanin does not correlate with skin pigmentation, a similar amount of this pigment is observed in the dark and light skin. While in hair, the ratio of eumelanin to pheomelanin decides about the color [35]. Eumelanin comparing to pheomelanin has better photoprotecting properties – higher resistance to degradation and ability to reactive oxygen species (ROS) neutralization [44]. Eumelanins are considered to be more effective in terms of photoprotection than the reddish pheomelanin. As a consequence, the risk of skin cancer in lighter skin is 30-40-fold higher than in the darker one [41]. Products of genes regulating melanogenesis act at subcellular, cellular, tissue and environmental levels [21]. During melanogenesis, as intermediate products, cytotoxic molecules are synthesized (quinones, hydrogen peroxide). Thus, melanocyte protects itself by separating areas of melanogenesis in melanosomes and increases the level of antiapoptotic protein Bcl-2 [1, 21].