The Regulation of Skin Pigmentation

Abstract

Visible pigmentation of the skin, hair, and eyes depends primarily on the functions of melanocytes, a very minor population of cells that specialize in the synthesis and distribution of the pigmented biopolymer melanin. Melanocytes are derived from precursor cells (called melanoblasts) during embryological development, and melanoblasts destined for the skin originate from the neural crest. The accurate migration, distribution, and functioning of melanoblasts/melanocytes determine the visible phenotype of organisms ranging from simple fungi to the most complex animal species. In human skin, melanocytes are localized at the dermal/epidermal border in a characteristic regularly dispersed pattern. Each melanocyte at the basal layer of the epidermis is functionally connected to underlying fibroblasts in the dermis and to keratinocytes in the overlying epidermis. Those three types of cells are highly interactive and communicate with each other via secreted factors and their receptors and via cell/cell contacts to regulate the function and phenotype of the skin. Overview: Architecture of the SkinEpidermal melanocytes occur at an approximate ratio of 1:10 among basal keratinocytes and distribute the melanin they produce to ϳ40 overlying suprabasal keratinocytes via their elongated dendrites and cell/cell contacts (presented schematically in Fig. 1). Although melanocytes and stem cell keratinocytes in the basal layer of the epidermis are very stable populations that proliferate extremely slowly under normal circumstances, keratinocytes in the upper layers of the epidermis proliferate relatively rapidly. That upward pressure carries them toward the surface of the skin along with their ingested melanin to form a critical barrier for the organism against the environment and the many stresses that originate there. Thus it is not the melanin within melanocytes only, but in combination with the pigment in more superficial layers, that gives skin its characteristic color. Although melanocytes in other locations of the body (e.g. hair follicles, eyes, inner ear, etc.) interact with surrounding cells in manners distinct from those in the epidermis, the basic processes involved in producing the melanin and the organelles within which it is synthesized (termed melanosomes) are comparable, as are the factors that regulate melanogenesis. This review will restrict itself to epidermal pigmentation, and readers interested in factors influencing pigmentation at other sites should consult recent reviews (1-6) and books (7, 8) on those topics.

Variations in skin colour and the biological consequences of ultraviolet radiation exposure

“…[1][2][3][4][5][6] Human skin colour is determined by the total quantity of melanin, the proportion between the brown-black eumelanin and the yellow-red pheomelanin, and its distribution through the epidermis. [7][8][9] The type and amount of melanin is under the control of several genes with a great number of alleles, resulting in wide variations of skin colours. Assessment of skin colour according to Fitzpatrick's phototype classification system, originally created for caucasian skin and based on self-reported erythema sensitivity and tanning ability, 10 is extensively used by dermatologists, despite limitations in relation to quantification and reliability.…”

Sesamol decreases melanin biosynthesis in melanocyte cells and zebrafish: Possible involvement of MITF via the intracellular cAMP and p38/JNK signalling pathways

“…Melanogenesis is modulated by several factors, including UV irradiation, alpha‐melanocyte‐stimulating hormone ( α ‐MSH) 7, forskolin, stem cell factor (SCF) 8, wnt‐3a 9 and isobutylmethylxanthine (IBMX) 10, within intracellular melanosomes in the melanocytes 11. Stimulation of the melanocortin 1 receptor (MC1R) by α ‐MSH activates adenyl cyclase through G protein signalling, which subsequently increases cyclic adenosine monophosphate (cAMP) production.…”

Cancer immunology and canine malignant melanoma: A comparative review

“…Although differentiation antigens are shared between normal and tumour tissues, they are recognised as a bona fide target of cancer immunotherapy with the caveat that successful vaccination can cause auto-immunity (Buonaguro et al, 2011;Weber et al, 1998). Tyrosinase (a melanosomal glycoprotein) is a differentiation antigen with expression confirmed in canine melanocytic neoplasms ( Figure. 1) (Brichard et al, 1993;Ramos-Vara and Miller, 2011;Yamaguchi et al, 2007). Its key role in melanogenesis means that tyrosinase represents a valid target for anti-melanoma immunotherapeutics.…”