The colour of hair is variable. It is important in many mammals for camouflage and in human beings for making hair visible, such as the increased colour of sexually related hair after puberty [17,18]. Loss of hair pigment resulting in greying and whitening of hair is one of the first characteristics of ageing. Within the hair follicle, neural crest-derived melanocytes in the hair bulb produce and transport melanin to the keratinocytes of the precortical zone that differentiate to form the pigmented hair shaft. The hair follicle pigmentary unit in the bulb cyclically regenerates synchronously with the hair follicle during the hair cycle. The melanogenic activity of the follicular melanocytes is strictly coupled to the anagen
stage, decreases during late anagen and early catagen, and ceases during late catagen and telogen [26,92,93].
In the anagen hair follicle, melanocytes are divided into three distinct subpopulations. The first population 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 [26,36,94]. The second population is located in the hair follicle outer root sheath and represents differentiating melanocytes. The third is located in the hair matrix above the dermal papilla and actively produces melanin [26,93] (Fig. 1.5). Melanogenesis is controlled by several key enzymes that are uniquely expressed in the melanocytes (reviewed in [95] ). Tyrosinase catalyses the rate-limiting initial events of melanogenesis, and mutations in tyrosinase gene lead to loss of pigment [96]. Tyrosinase-related proteins (TRP) 1 and TRP2 share 40-45% amino acid identity with tyrosinase and are also critically important for melanogenesis, functioning as downstream enzymes in the melanin biosynthetic pathway [97].
Hair pigmentation is tightly regulated by several hormones and growth factors. Androgens play a major role in causing alterations of human hair colour, including increase of pigment during vellus to terminal hair switches in many regions such as the beard after puberty, or the converse on the scalp during male pattern balding [98]. Changes in anagen – associated melanogenesis are accompanied by changes in the gene expression of melano- cortin 1 receptor (MC1-R) activated by POMC-derived ACTH and MSH peptides [99], and ACTH and a-MSH are able to promote human follicular melanocyte differentiation by
Melanocyte
 |
Undifferentiated
melanocytes
Differentiated pig men t-producing melanocytes
Figure 1.5 Hair follicle melanocyte distribution. Schematic drawing represents localisation of different subpopulations of melanocytes in the anagen hair follicle. Melanocyte stem cells are located in the bulge, the differentiating melanocyte are mostly located in the outer root sheath, while differentiated melanogenically active melanocytes are present in the hair bulb.
up-regulating melanogenesis, dendricity, and proliferation in less differentiated melanocyte subpopulations [100]. SCF/c-kit signalling is required for cyclic regeneration of the hair pigmentation unit. Pharmacological inhibition of SCF/c-kit signalling in vivo leads to the production of depigmented hairs in rodents [26]. In addition, other proteins known to be involved in melanocyte biology, including agouti signal protein, the endothelin family, fibroblast growth factor 2, and hepatocyte growth factor may be important for modulating the activity of hair follicle melanocytes during the hair cycle (reviewed in [101,102]).