FIGURE 15.8 • Formation of melanin pigment and secretion of pigment granules into keratinocytes. Melanocytes produce membrane-bounded structures that originate in the Golgi apparatus as premelanosomes. a. Within the early melanosomes, as maturation proceeds, melanin is produced from tyrosine by a series of enzymatic reactions. b. Mature melanosomes and their melanin contents are transferred to neighboring keratinocytes by pigment donation, which involves the phagocytosis of the tips of the melanocyte. c. In darker skin (on the right), the melanin is degraded slowly, and melanosomes remain discrete; in lighter skin (on the left), the melanin is degraded more rapidly d. through the process of macroautophagy. (Based on Weiss L, Greep RO. Histology. New York: McGraw-Hill, 1977.) tors, including major genetic determinants, several modifier genes, and environmental influences such as exposure to ultraviolet radiation and gender effects. The most signifi-cant is melanin content. Although the number of melanocytes is essentially the same in all races, the fate of the melanin that is produced by the melanocytes differs. For example, because of the lysosomal activity of the ker-atinocytes, melanin is degraded more rapidly in individuals with light skin than in individuals with dark skin. In the former, melanosomes are more concentrated in the ker-atinocytes nearest the basal layer and are relatively sparse in the midregion of the stratum granulosum. In contrast, dark skin may exhibit melanosomes throughout the epider-mis, including the stratum corneum. In addition, melanin pigment comprises two distinct forms. One form, eumelanin, is a brownish black pigment. The other form, pheomelanin, is a reddish yellow pigment. Each is genetically determined. Coloration is most appar-ent in hair because of the concentration of melanin pig-ment granules, but it is also reflected in skin coloration. Exposure to ultraviolet radiation, particularly the sun’s rays is called tanning. It increases the number of melanocytes and accelerates the rate of melanin produc-tion, thus protecting against further radiation effects. Response to ultraviolet radiation is genetically determined and is more pronounced in individuals with darker color of skin. Increased pigmentation of the skin may also result from hormonal imbalance—for example, in Addison’s disease. Lack of pigmentation occurs in a condition known as albinism. In this hereditary condition, premelanosomes are produced by melanocytes, but because of the absence of dihydroxyphenylalanine (DOPA) and the subsequent trans formation of DOPA into melanin fail to occur. Thus, there is no pigmentation in the skin or hair of these individuals. Two genes—Bcl2 and Mitf—appear to be responsible for the process of graying. The expression of Bcl2 in melanocyte stem cells is essential to maintaining their population within the niche of the follicular bulge. Defi-ciency in Bcl2 expression causes apoptosis of melanocyte stem cells and a consequent decrease in the number of melanocytes. Melanocyte depletion occurs with age, resulting in a decreased rate of pigment donation to keratinocytes. Therefore, the skin becomes lighter with increased age, and the incidence of skin cancer also increases. Melanocyte depletion caused by defective self-maintenance of melanocyte stem cells is also linked to hair graying, the most obvious sign of aging in humans. Individ-uals with a mutation in the Bcl2 gene may become prema-turely gray. Other normal factors that affect skin coloration include the presence of oxyhemoglobin in the dermal vascular bed, which imparts a red hue; the presence of carotenes, an ex-ogenous orange pigment taken up from foods and concen-trated in tissues containing fat; and the presence of certain endogenous pigments. The latter include degradation products of hemoglobin, iron-containing hemosiderin, and iron-free bilirubin, all of which impart color to the skin. Hemosiderin is a golden brown pigment, whereas bilirubin is a yellowish brown pigment. Bilirubin is normally removed from the bloodstream by the liver and eliminated via the bile. A yellowish skin color as a result of abnormal accumu-lation of bilirubin reflects liver dysfunction and is evidenced as jaundice.