Human skin pigmentation: melanocytes modulate skin color in response to stress

Abstract

All organisms, from simple invertebrates to complex human beings, exist in different colors and patterns, which arise from the unique distribution of pigments throughout the body. Pigmentation is highly heritable, being regulated by genetic, environmental, and endocrine factors that modulate the amount, type, and distribution of melanins in the skin, hair, and eyes. In addition to its roles in camouflage, heat regulation, and cosmetic variation, melanin protects against UV radiation and thus is an important defense system in human skin against harmful factors. Being the largest organ of the body that is always under the influence of internal and external factors, the skin often reacts to those agents by modifying the constitutive pigmentation pattern. The focus of this review is to provide an updated overview of important physiological and biological factors that increase pigmentation and the mechanisms by which they do so. We consider endocrine factors that induce temporary (e.g., during pregnancy) or permanent (e.g., during aging) changes in skin color, environmental factors (e.g., UV), certain drugs, and chemical compounds, etc. Understanding the mechanisms by which different factors and compounds induce melanogenesis is of great interest pharmaceutically (as therapy for pigmentary diseases) and cosmeceutically (e.g., to design tanning products with potential to reduce skin cancer risk).

Structure and Function of Human Tyrosinase and Tyrosinase‐Related Proteins

“…[5] The relative amount of melanin is ak ey determinant of colorbased ethnic diversification in humans. [6] In humans, melanin is synthesized in melanosomes,w hich are organelles inside specialized cellss uch as melanocytes in skin and hair,a nd retinal pigmente pithelium cells in the eye. [7] Three tyrosinase-like enzymes take part in its biosynthesis, tyrosinase( TYR) and tyrosinase-related proteins 1a nd 2( TYRP1 and TYRP2).…”

“…In addition, TYR and TYRP1 variants are significantly associated with risk of melanoma, am alignant tumor of melanocytes that causes the majority of deathsr elated to skin cancer. [8] On the otherh and, excessm elanin production or abnormal distribution can cause pigmentation disorders, such as over-tanning, age spots and melasma, [6] which has prompted the development of skin-whitening compounds to reduce the melanin content. Furthermore,i nhibition of melanin synthesis is being considered as av alid therapeutics trategy for the treatment of advanced melanotic melanomas.…”

Down-regulation of tyrosinase, TRP-1, TRP-2 and MITF expressions by citrus press-cakes in murine B16 F10 melanoma

“…In addition, tyrosinase-related protein (TRP)-1 and TRP-2 are major targets of melanogenic enzymes induced by MITF. TRP-2 catalyzes the rearrangement of dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA), whereas TRP-1 oxidizes DHICA to a carboxylated indole-quinone, which is eventually converted into melanin [6,[7][8][9] . Hence, downregulation of tyrosinase activity has been proposed to be responsible for reduced melanin production.…”

“…Cellular tyrosinase activity was measured by the method of Yen (1) rutin, (2) narirutin, (3) naringin, (4) hesperidin, (5) neohesperidin, (6) neohesperidin dihydrochalcone, (7) naringenin, (8) hesperetin, (9) aprgrnin, (10) nobiletin, (11) tangeretin, (12) auraptene was diluted with ethanol to obtain a series concentration of working solutions, and subjected to HPLC analysis.…”

Inhibitory Effect of Elephantopus mollis H.B. and K. Extract on Melanogenesis in B16 Murine Melanoma Cells by Downregulating Microphthalmia-Associated Transcription Factor Expression

“…4,5) Melanogenesis begins with extracellular stimuli, such as UV light, X-rays, and chemicals, including -melanocyte-stimulating hormone ( -MSH). 6) The enzymes tyrosinase (TYR), tyrosinase-related protein 1 (TRP1), and tyrosinase-related protein 2 (TRP2), collectively referred to as the tyrosinase gene family, are essential in the overall production of melanin. [7][8][9][10][11] TYR is the key enzyme in the synthesis of the two types of melanin, black-brown eumelanin and redyellow pheomelanin.…”