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Effects Of Glucocorticoids, Retinoic Acids And Asiaticoside On Melanogenesis In Melanocytes

Posted on:2004-03-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:D LiuFull Text:PDF
GTID:1104360092495546Subject:Dermatology and Venereology
Abstract/Summary:PDF Full Text Request
Human skin color is the net result of different combinations and concentrations of blue(reduced hemoglobin), red(oxyhemoglobin), yellow(carotenoids and flavins), and brown(melanin). The most significant component in the determination of skin color is the pigmented product of the melanocyte, melanin, which may be either brown-black (eumelanin) or yellow-red(pheomelanin). Melanin has a variety of important functions: (1) as a cosmetic entity ? participating in protective coloration and in sexual attraction with species, (2) as a barrier against ionizing radiation ?especially important with respect to protection against ultraviolet light irradiation, (3) as a potential scavenger of cytotoxic radicals and intermediates, and (4) as a participant in developmental processes ?particularly relating to neurological development. Melanin pigmentation in human skin may be divided into constitutive and facultative skin colors. Constitutive, or intrinsic, skin color is a genetically determined degree of cutaneous melaninpigmentation, which is present independent of outside influences. Facultative(inducible) skin color represents the increased melanin pigmentation above that of the constitutive level; and other environmental factors upon the individual's genetically endowed melanogenic potential. Production of melanin is one of the most well known differentiation features of melanocytes, which is a process consists of many steps of biochemical enzyme-catalyzed reactions and is regulated complicated and precised. Tyrosinase activity is a key determinant of melanin production in the skin. This enzyme catalyses the early rate-limiting steps of the biosynthetic pathway of melanin: the hydroxylation of tyrosine and the oxidation of dopa . Moreover, the rate of melanin synthesis is correlated with the amount and activity of tyrosinase in the cells . In addition, a positive relationship exists between human skin color and the activity of this enzyme. Melanin production appears to be regulated by a subtle balance between positive (tyrosinase, TRP-1, TRP-2) and negative (melanogenic inhibitors) melanogenic factors. TRP-1 shares the two catalytic properties ascribed to tyrosinase In addition, a positive correlation between the synthetic rate of TRP-1 and the melanin formation has been reported in mouse melanoma cells. As to TRP-2, this enzyme catalyzes the conversion of DOPAchrome to DHICA 5,6-dihydroxyindole-2-carboxylic acid) and seems to play a key role in the control of the distal steps of the melaninpathway synthesis .Melanocyte located in the basal layer of epidermis are highly responsive cell that continually sample their environment and modulate their behavior accordingly. As an integral part of the multicellular epidermal environment, melanocyte interact functionally with the cells of the epidermis. Melanocytes transfer melanosomes to surrounding keratinocytes, creating a system of protection against UV radiation. Keratinocytes, the major cellular component of the epidermis, contribute many of the mediators which influence melanocyte function. Melanocyte proliferation, pigment production, adhesion, and migration are controlled by cytokines, inflammatory mediatiors, growth factors, and matrix components synthesized and secreted by keratinocytes, Langerhans cells, and fibroblasts. In turn, melanocytes are also the source of mediators which can influence inflammation.With the development of melanocyte biology and mechanisms for regulation of melanogenesis , advances in treatment of pigmentary diseases have been gained. Several therapeutic modalities are now available for pigmentary disease such as vitiligo and melasma. However, the number of treatment options that are available for a wide range of pigmentary diseases and curative effects are not satisfied. In the present study, we investigate effects of three kinds of compounds ( glucocorticoids, retinoic acid and asia...
Keywords/Search Tags:Glucocorticoids,
PDF Full Text Request
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