1-7-10 Melanocytes and pigmentation 1. Learn the basic elements of pigmentation of the skin.

The following dermal pigments give the following skin colorations: Collagen white Melanin* brown, blue Extraneous pigment tattoo and FB Silver (Argyria) blue, gray (occurs with Thorazine antipsychotic) Lipids (xanthomas) yellow Carotene/lipochromes yellow Cells brown, purple, yellow, violet *Melanin hearts drugs. Its an electron acceptor, while drugs are an electron donor. Such drugs include cocaine, epinephrine, dopamine, phenothiazines, and chloroquine. The development of melanocytes: Melanoblasts migrate from neural crest epidermis in fetal life They start out as clear dendritic cells that then produce melanosomes, which are organelles that are transferred to keratinocytes. Melanosomes contain tyrosinase, a copper-containing enzyme that is normally kept inactived by SH. It is activated by UV and heavy metals (which destroy SH) and produces the melanin chromoprotein. Melanosomes go through TODA stages TODA stage I: spherical membrane containing lots of tyrosinase, no melanin TODA stage II: oval with filament periodicity TODA stage III: start seeing some melanin TODA stage IV: electron opaque from melanin. No tyrosinase is left. Melanosomes migrate from perinuclear area to dendrite tips and are transferred to keratinocytes (see melanocyte-keratinocyte unit concept below) UV light stimulates the proliferation of melanocytes The density of melanocytes is highest in the head, dorsal foot, and scrotum. Melanin is removed via three mechanisms: desquamation of keratinocytes. Melanosomes are degraded in keratinocytes within lysosomes Melanin diffusion back into the dermis, where the pigment is phagocytosed by macrophages and removed via lymphatics. 2. Learn the vocabulary of pigmentation. Melanocytes are the dendritic cells in the epidermis that make pigment accounting for the various hues of skin color. Melanosomes are oval structures within melanocytes that are intracellular organelles that are the sites of melanin production. Tyrosinase is the critical enzyme in melanosomes that make melanin.

3. Understand the differences in pigmentation in light skin versus dark skin. The number of melanocytes is the same in blacks and whites. It is the SIZE of melanosomes that is differentthey are (of course) larger in blacks than in whites. Melanosomes in dark-skinned individuals appear as single dark entities, while they appear as vacuole-bound groups in white skin. Melanosomes are also more easily degraded in white skin. So in essence, skin color differences are due to melanosome size, number, packaging, distribution, and processing. Melanocyte number is the same regardless of skin color. 4. Understand the melanocyte-keratinocyte unit concept. Melanosomes are passed from melanocytes to keratinocytes. One melanocyte is arborized to roughly 35 keratinocytes (each melanocyte extends dendrites to touch keratinocytes). 5. Appreciate how disease and other factors can influence skin hue. As we know, vasodilation causes erythema while vasoconstriction causes pallor. With that in mind, hemangiomas cause congenital blood vessel abnormalities (ERYTHEMA) while nevus anemicus causes congential vasoconstriction (PALE MACULES) Skin response to UVL occurs in two ways (immediate and delayed): Immediate pigment darkening: occurring in seconds, it involves dislocation of melanosomes to dendrites. There is NO INCREASE IN MELANOCYTE NUMBER. Delayed pigment formation: occurring over 2-3 days, it involves increased melanosomes in melanocytes, increased melanosomes in keratinocytes, and INCREASED MELANOCYTE NUMBER. Melanocyte stimulating hormone (MSH) stimulates melanization. There are two forms: Alpha MSH, which is basic and has 13 aas Beta MSH, which is acidic and has 18-22 aas MSH is held in check by adrenal cortical hormones (ACTH) and is increased in Addisons, Pituitary tumors, acromegaly, and puberty.