Disorders of Pigmentation
Ayşe Serap Karadağ, Lawrence Charles Parish, Jordan V. Wang in Roxburgh's Common Skin Diseases, 2022
Overview: Melanocytes are dendritic cells derived from the neural crest. They are located in the basal layer of the epidermis but may also be observed in the eye, inner ear and leptomeninges of the brain. Melanocytes serve three important functions: production of melanin, protection from ultraviolet-associated mutations, and absorption of ultraviolet radiation (UVR). Melanin is derived from phenylalanine and passes through several steps before forming pheomelanin, eumelanin, or neuromelanin (Figure 25.1). Pheomelanin produces yellow-red pigment, and eumelanin produces brown-black pigment. The process of determining which pigment is produced is controlled by the melanocortin-1 receptor (MC1R). A loss of function in this receptor leads to increased production of pheomelanin and can increase the risk of melanoma from ultra-violet radiation. Genetic variations in the MC1R gene have been identified in malignant melanoma and oculocutaneous albinism. Melanin synthesis is controlled by the melanocyte-stimulating hormone (MSH), which is derived from propiomelanocortin (POMC). POMC is also the precursor for adrenocorticotropic hormone (ACTH), which is raised in Addison’s disease. This accounts for the cutaneous hyperpigmentation seen in this condition. Once synthesized, melanin is then packaged into melanosomes and transported to neighboring keratinocytes. Higher Fitzpatrick phototypes have increased melanocyte size and distribution rather than increased melanocyte density.
Lumps and bumps
Michael Gaunt, Tjun Tang, Stewart Walsh in General Surgery Outpatient Decisions, 2018
Most suspicious pigmented lesions are referred to a dermatology or plastic surgery clinic for excision if malignancy is suspected. However, knowledge of these lesions is necessary for the general surgeon as they may be referred as simple skin lesions for day-case excision without the appreciation that they may be malignant, especially if not pigmented. Melanocytes are specialised cells located at the basal layer of the epidermis. They synthesise melanin and store it in vesicles called melanosomes. Melanosomes are distributed to surrounding cells. Melanin production is stimulated by sunlight and a pituitary hormone, melanocyte-stimulating hormone (MSH). All races have approximately the same number of melanocytes, but the baseline activity of these cells varies. Naevus cells are melanocytes that have entered the dermis and have a distinct pheno-type. They are more spherical, have fewer dendritic processes and display aggregation in nests.
The skin’s endogenous antioxidant network
Roger L. McMullen in Antioxidants and the Skin, 2018
As discussed in Chapter 1, melanocytes are specialized cells capable of synthesizing melanin, which is a pigment responsible in part for the color of our skin and hair. Molecules of melanin are packed in cellular organelles known as melanosomes. In the epidermis of skin, melanosomes are transferred from melanocytes to keratinocytes in order to provide protection to the nucleus, hence DNA, of these cells. In the mature hair shaft, melanin exists as granules in the cortex protecting the keratin intermediate filaments, which confer the fiber with its great tensile strength. There are two types of biological melanin present in skin and hair: eumelanin and pheomelanin (Figure 3.23).38Eumelanin is responsible for dark color pigmentation and results in brown and black tones. Pheomelanin, on the other hand, is a red and yellow pigment and is more predominantly found in fair-skinned individuals, e.g., individuals with red hair contain greater quantities of pheomelanin than eumelanin. The synthesis of both types of melanin begins with the aromatic amino acid tyrosine in a reaction that is catalyzed by the enzyme, tyrosinase. This results in the formation of 3,4-dihydroxyphenylalanine (DOPA) which further undergoes conversion to dopaquinone. At this point, two separate reaction pathways proceed for the synthesis of eumelanin and pheomelanin (see Appendix 2 for a schematic of melanin synthesis). With its highly conjugated structure, melanin is a highly efficient absorber of UV and visible light with an absorption profile that is extremely high at low wavelengths (UV region) and decreases monotonically with increasing wavelengths into the visible region of the electromagnetic spectrum.
Postinflammatory hyperpigmentation secondary to external insult: an overview of the quantitative analysis of pigmentation
Published in Cutaneous and Ocular Toxicology, 2013
Sonia A. Lamel, Maral Rahvar, Howard I. Maibach
Context: Despite new technologies, few studies have quantified changes in melanocyte numbers associated with postinflammatory hyperpigmentation (PIH) secondary to exogenous causes. Objective: This article aims to review what is known about the pathogenesis of PIH secondary to external insults and its relationship to the resultant degree of quantitative changes in melanocytes. Methods: We performed a review of articles exploring PIH resulting from external cutaneous insults retrieved through database searching. We reviewed relevant articles for the pathogenesis, histopathology, and quantitative changes in melanocytes related to specific etiologies of PIH. Methodologies to quantify pigmentation changes in dermatologic conditions with clinical hyperpigmentation were also explored. Results: Significant increases in melanocyte counts of irritant affected skin is seen compared with melanocyte counts of unaffected skin. An increase in melanocyte counts was also found for spontaneous inflammatory dermatoses, even in the absence of clinical hyperpigmentation. Furthermore, changes in melanocyte density and appearance are also seen secondary to inflammation. In addition, increases in epidermal melanocytes are seen with cutaneous exposure to certain agents, and melanocyte increases vary by exposure agent. Conclusions: The degree of hyperpigmentation related to the intensity and duration of exposure to the causative factors of PIH is essential to better understand the pathophysiology of the disease process. The application of new methodologies to determine quantitative changes in melanocytes elicited by specific causative inflammatory agents has implications to prevent PIH, add to knowledge about disease duration, to develop better treatments for PIH, and to aid our understanding of the biology of the melanocyte.
Effects of hydroxybenzyl alcohols on melanogenesis in melanocyte-keratinocyte co-culture and monolayer culture of melanocytes
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2008
Szu-Hsiu Liu, I-Ming Chu, I-Horng Pan
In mammalian skin, melanocyte proliferation and melanogenesis can be stimulated by keratinocytes, fibroblasts and other regulatory factors. To determine whether hydroxybenzyl alcohols (HBAs) show more inhibitory in melanocytes cultured alone or in melanocytes co-cultured with keratinocytes, we developed a murine melanocyte–keratinocyte co-culture model to investigate the pigmentation regulators in company with other melanogenic inhibitors and stimulators. It was found that the effects of HBAs and melanogenic factors were more evident in melanocytes co-cultured with keratinocytes. Keratinocytes may play a synergistic role in melanocyte melanogenesis and influence the pigment production. The tests in the co-culture model also imply that the inhibitory effects of HBAs on melanogenesis are due to the direct inhibition of melanosomal tyrosinase activity. HBAs showed a low cytotoxicity. The eventual results proved that HBAs are promising and safe agents for skin whitening in melanocyte alone and in co-culture systems. The co-culture model provides a more physiologically realistic condition to study the interaction between melanocytes and keratinocytes, which enables a reliable screening system for depigmenting compounds.
Darkening with UVRAG
Published in Autophagy, 2019
Shun Li, Gyu-beom Jang, Christine Quach, Chengyu Liang
ABSTRACT Ultraviolet radiation (UVR)-induced skin pigmentation, afforded by the dark organelles termed melanosomes, accounts for the first-line protection against environmental UVR that increases the risk of developing skin cancers including melanoma. We have recently discovered that UVRAG, originally identified as a BECN1-binding macroautophagy/autophagy protein, appears to have a specialized function in melanosome biogenesis beyond autophagy through its interaction with the biogenesis of lysosome-related organelles complex 1 (BLOC-1). This melanogenic function of UVRAG is controlled by the melanocyte-specific transcription factor MITF as a downstream effector of the α-melanocyte-stimulating hormone (α-MSH)-cAMP signaling in the suntan response, which is compromised in BRAF mutant melanoma. Thus we propose a new mode of UVRAG activity and regulation in melanocyte biology that may affect melanoma predisposition.
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