The factor most important to determining the hair follicle sensitivity to laser treatment is the melanin pigment of the hair follicle. Therefore understanding when, where, and how melanin is formed is important in understanding laser efficiency, as well as in determining the temporary or permanent effect of laser on hair reduction. Hair color is determined by the concentration and type of melanin, which is synthesized in the melanocytes. There are two major types of melanin: the black/brown eumelanin and the reddish/yellow pheomela – nin. The presence of different amounts or a combination of eumelanin and pheomelanin result in the variety of hair color. While pheomelanin is the major melanin type in red hair, eumelanin is present in large amounts in brown and black hair. Melanin synthesis in hair follicles is carried out by melanocytes present on the basement membrane surrounding the dermal papilla. The formed melanin is transported to the keratinocytes in the precortical zone that differentiate to form the pigmented hair shaft. Thus, the melanocytes together with hair matrix keratinocytes and dermal papilla fibroblasts form the hair follicle pigmentary unit. Melanogenesis is controlled by several key enzymes that are uniquely expressed in melanocytes [38]. Tyrosinase catalyzes the rate-limiting initial events of melanogenesis, and mutations in tyrosinase gene lead to loss of pigment. Tyrosinase-related proteins (TRP) 1 and TRP2 share 40-45% amino acid identity with tyrosinase and are also important in the melanogenesis process, functioning as downstream enzymes in the melanin biosynthetic pathway [38,39]. The TRP1 appears to be important for eumelanogenesis, as suggested by its lack or defective expression in pheomelanogenic cells [38]. Melanin synthesis occurs in specialized organelles, termed melanosomes, which are transferred from melanocytes to the surrounding keratinocytes upon their maturation [39]. Melanosome structure correlates with the type of melanin produced—eumelanosomes are elliptical and contain fibrillar matrix, whereas the pheomelanosome shape is variable, but predominantly spherical and contain a vesiculoglobular matrix. The size of the melanosomes and their numbers are important in determining pigmentation. In black hair, follicular melanocytes contain the largest number of melanosomes, while in brown hair follicle melanosomes are slightly smaller, and in blonde hair melanosomes are poorly melanized.
Hair is actively pigmented only during the anagen stage of the hair cycle. The hair follicle pigmentary unit cyclically regenerates synchronously with the hair follicle transition through distinct hair cycle stages [40]. The melanogenic activity of the follicular melanocytes is strictly coupled to the anagen stage, decreases during late anagen and early cata – gen, and ceases during late catagen and telogen (Fig. 9.2) [41]. In anagen hair follicle, the melanocytes may be divided into three distinct subpopulations. The first is located in the hair follicle bulge and represents melanocyte stem cells that repopulate the melanocytes in the new hair bulb formed at the onset of anagen [23,42]. Melanocytes have their own distinct population of stem cells responsible for their regeneration. These stem cells are characterized by the expression of Trp2, Bcl-2, Pax3, with extremely low proliferation rate. Bcl-2 appears to play a key role in the maintenance of melanocyte stem cells, as Bcl-2 knockout mice show progressive hair graying due to the depletion of melanocyte stem cells [43,44]. The second population of follicular melanocytes is located in the hair follicle outer root sheath, expresses TRP2 and relatively weak TRP1, displays proliferative activity during early and mid-anagen, and represents differentiating melanocytes. The third population represents melanogenically-active melanocytes, which are located in the hair matrix above the dermal papilla [23]. These cells proliferate only during mid-anagen, and express a full set of enzymes and other proteins involved in melanin biosynthesis including tyrosinase, Trp1, Trp2 (in mice), and pMel17 (in humans). They actively produce melanin during mid – to late anagen, and transport it to hair-shaft keratinocytes. During catagen, melanocytes progressively disappear from the hair bulb, presumably via apoptosis and/or dedifferentiation [45-47].
The epidermis also contains pigment-producing melanocytes. However, follicular melanocytes show several important differences from the epidermal melanocytes. They are larger, have more extensive dendrites, and contain a greater number and larger size melano- somes, compared to epidermal melanocytes. In addition, the hair bulb melanin unit consists of one melanocyte to five keratinocytes in the hair bulb as a whole, and one to one in the basal layer of the hair bulb matrix, whereas each epidermal melanocyte is associated with about 36 viable keratinocytes. This differentiation is primarily responsible for the selective photothermolysis advantage in favor of hair removal, while sparing the epidermis.