毛囊色素

毛发的颜色主要取决于毛囊色素(优黑素/褐黑素)的合成与表达,黑素颗粒由黑素细胞合成,并向皮质及角质形成细胞转运,最终沉积于毛干内,上述过程主要包括了毛囊黑素细胞的发育,黑素颗粒在毛囊中的合成和转运,黑素细胞的调控,黑素颗粒在毛干上的沉积以及毛囊色素单元的老化。     

皮肤科学基础

20072714皮肤黑素转运的调节机制(综述)/罗增香(复旦大学附属华山医院皮肤科),项蕾红∥国际皮肤性病学杂志.-2007,33(4).-236~238正常的皮肤颜色是由高效的黑素合成和正确的黑素转运决定的,两者之中任一环节出现问题都会导致色素障碍性疾病的发生。概述了皮肤黑素转运的调控、黑素在毛囊中的转运以及紫外线照射对黑素转运的影响,提示研究黑素转运为探讨色素障碍性疾病的发病机制提供了理论依据,并最终帮助我们在治疗上寻找到新的途径。参24(樊靖华)20072715白芷不同提取物对黑色素影响的比较研究/周典(上海中医药大学),张建华,李华…∥上海…     

黑素核在黑素转运与降解中的作用

【摘要】 黑素变化调节着皮肤颜色深浅。既往研究认为，黑素转运存在胞吐-胞吞、脱落-吞噬、细胞吞噬、膜融合四种途径，黑素小体是黑素转运的主要载体。新近研究显示，依赖于胞吐-胞吞途径的黑素核在黑素转运中具有重要作用。本文综述了黑素核转运中黑素细胞胞吐、角质形成细胞胞吞过程及转运后在角质形成细胞内的降解过程，为难治性色素性疾病提供新的治疗方向。     

在重建色素沉着表皮中角质形成细胞的黑素小体帽化——紫外线照射和异丁基甲黄嘌呤对黑素生成的影响

表皮黑素细胞的主要功能是生成黑素并将其转移至相邻的角质形成细胞。黑素可以保护细胞免受外界有害辐射的伤害,黑素的生成和转运由复杂的调控机制控制。白癜风等色素性疾病表现明显的黑     

毛球部黑素细胞黑素合成开关

毛球部黑素细胞呈毛发生长周期依赖性合成黑素。当毛发进入生长期 ,黑素小体、酪氨酸酶、酪氨酸酶相关蛋白 1、酪氨酸酶相关蛋白 2渐趋成熟 ,催化黑素生化合成反应 ,并通过树突向前皮质细胞输送成熟黑素小体 ,使毛发着色同时还能影响毛囊生长、毛干形成及中胚层组织重塑。生长期末 ,酪氨酸水平降低 ,毛球部黑素细胞停止合成黑素     

Rab蛋白在黑素小体合成及转运中的作用

Rab蛋白家族是小G蛋白超家族中最大的亚家族,广泛存在于动物、植物和微生物等真核生物中,是囊泡运输重要的调节因子,具有调节囊泡的靶向运输、囊泡的拴系、与靶膜泊位与融合、囊泡的芽生等作用。皮肤的颜色与黑素小体的合成和转运密切相关。哺乳动物的Rab蛋白大约有60种,其中的Rab32/38和Rab9a在黑素小体的合成过程中发挥了重要作用;Rab27a、Rab21、Rab17及Rab36在黑素小体的转运过程中具有重要意义;Rab7及Rab11即参与了黑素小体的合成,又参与了黑素小体转入角质形成细胞的过程。因此,这些Rab蛋白基因的突变将会引发相应的遗传性色素性疾病。     

毛球部黑素细胞黑素合成开发

毛球部黑素细胞呈毛发生长周期依赖性合成黑素。当毛发进入生长期，黑素小体、酪氨酸酶、酪氨酸酶相关蛋白－1、酪氨酸酶相关蛋白－2渐趋成熟，催化黑素生化合成反应，并通过树突向前皮质细胞输送成熟黑素小体，使毛发着色同时还能影响毛囊生长，毛干形成及中胚层组织重塑。生长期末，酪氨酸水平降低，毛球部黑素细胞停止合成黑素。     

皮肤黑素转运的调节机制

黑素是决定皮肤颜色的主要色素，它由黑素细胞合成。黑素细胞主要存在于皮肤和毛囊中，黑素在黑素小体内合成后，随其迁移到树突末端，树突朝邻近的角质形成细胞生长并释放。然后，黑素小体在多种分子的调节下，进入邻近的角质形成细胞，形成皮肤色素并起到有效的光防护作用。     

黑素小体转运机制的研究进展

色素的生物合成过程已基本明确,但黑素小体从黑素细胞转运至邻近的角质形成细胞的机制尚未完全明了.目前认为许多分子和信号转导途径参与此过程,如KGF、PAR-2、外源凝集素、拟糖蛋白、Rab-27a、肌球蛋白Va、Rho、Ca2+、cAMP/PK等,另外紫外线照射也影响黑素小体转运.了解黑素小体转运机制对于治疗色素异常疾病及开发美白产品有重要意义.     

~(14)C-2-硫脲嘧啶掺入显示:人毛囊色素单位可作为黑素生成调节剂的直接靶点

毛发色素由拉于毛乳头上部基底层中的一群黑素细胞合成,这些有活性的黑素细胞在黑素小体内生成黑素并将其转运至毛发纤维的前皮质角质形成细胞田(precortical kerationcyted).     

Hair follicle pigmentation

Hair shaft melanin components (eu- or/and pheomelanin) are a long-lived record of precise interactions in the hair follicle pigmentary unit, e.g., between follicular melanocytes, keratinocytes, and dermal papilla fibroblasts. Follicular melanogenesis (FM) involves sequentially the melanogenic activity of follicular melanocytes, the transfer of melanin granules into cortical and medulla keratinocytes, and the formation of pigmented hair shafts. This activity is in turn regulated by an array of enzymes, structural and regulatory proteins, transporters, and receptors and their ligands, acting on the developmental stages, cellular, and hair follicle levels. FM is stringently coupled to the anagen stage of the hair cycle, being switched-off in catagen to remain absent through telogen. At the organ level FM is precisely coupled to the life cycle of melanocytes with changes in their compartmental distribution and accelerated melanoblast/melanocyte differentiation with enhanced secretory activity. The melanocyte compartments in the upper hair follicle also provides a reservoir for the repigmentation of epidermis and, for the cyclic formation of new anagen hair bulbs. Melanin synthesis and pigment transfer to bulb keratinocytes are dependent on the availability of melanin precursors, and regulation by signal transduction pathways intrinsic to skin and hair follicle, which are both receptor dependent and independent, act through auto-, para- or intracrine mechanisms and can be modified by hormonal signals. The important regulators are MC1 receptor its and adrenocorticotropic hormone, melanocyte stimulating hormone, agouti protein ligands (in rodents), c-Kit, and the endothelin receptors with their ligands. Melanin itself has a wide range of bioactivities that extend far beyond its determination of hair color.     

Epilation today: physiology of the hair follicle and clinical photo-epilation

Despite the variations of length and type of hair (vellus or terminal), the growth of human hair in all body sites is cyclic. Phases of active hair growth, or anagen, are separated by periods of quiescence, or telogen. The duration of both phases varies greatly depending on the body site. Whether hairs are in anagen/telogen at the time of hair removal is important because only anagen hairs are particularly sensible to physical insults. Photo-epilation is a technique for long-term removal of unwanted hair by thermal destruction of the hair follicle and its reproductive system (stems cells). As melanin is the main chromophor existing in hair follicles the corresponding wavelength spectrum would range from ultraviolet up to infrared light. Furthermore longer wavelengths are preferred as the cromophor lies deep in the skin and the penetration of light is increasing with the wavelength. Thus, in the range of 600-1100 nm melanin absorption may be used for selective photothermolysis of hair follicles. Yet to be resolved questions for permanent destruction are the location of the key follicular target and the possible influence of the hair growth cycle on photothermolysis-induced hair removal. An overview on the individual physiology of the hair follicle is given to discuss the latest strategies for photo-epilation.     

A guide to assessing damage response pathways of the hair follicle: lessons from cyclophosphamide-induced alopecia in mice

After chemical, biological, or physical damage, growing (i.e. anagen) hair follicles develop abnormalities that are collectively called hair follicle dystrophy. Comparatively lower follicular damage induces the "dystrophic anagen" response pathway (=prolonged, dystrophic anagen, followed by severely retarded follicular recovery). More severe follicular damage induces the dystrophic catagen pathway (=immediate anagen termination, followed by a dystrophic, abnormally shortened telogen and maximally fast follicular recovery). In order to recognize these distinct damage response strategies of the hair follicle in a clinical or histopathological context, we have used the well-established C57BL/6J mouse model of cyclophosphamide-induced alopecia to define pragmatic classification criteria for hair follicle dystrophy (e.g., structure and pigmentation of the hair shaft, location, and volume of ectopic melanin granules, distension of follicular canal, number of TdT-mediated dUTP nick end labeling positive keratinocytes in the hair bulb; neural cell-adhesion molecule immunoreactivity and alkaline phosphatase activity as markers for the level of damage to the follicular papilla). These classification criteria for hair follicle dystrophy are useful not only in chemotherapy-induced alopecia models, but also in the screening of drug-treated or mutant mice in a highly standardized, accurate, sensitive, reproducible, easily applicable, and quantifiable manner.     

CD10 and CD34 in fetal and adult human hair follicles: dynamic changes in their immunohistochemical expression during embryogenesis and hair cycling

Background  CD10 and CD34 have been detected in both epithelial and mesenchymal components of anagen human hair follicles.
Objectives  To analyse the expression of CD10 and CD34 in human hair follicle development as well as in different phases of the hair cycle.
Methods  Fetal and adult hair follicles at different stages of the hair cycle were examined by immunohistochemistry for CD10 and CD34.
Results  In fetal follicles, CD10 is expressed by the cells of the placodes, and CD34 by the mesenchymal cells of the dermal condensate. As the follicle matures, CD10 can be seen in the matrix cells, inner root sheath and dermal sheath. In adult follicles, the expression of CD10 in the follicular epithelium is present in anagen follicles, but tends to disappear in catagen, and is not detected in telogen. The CD10 positivity of the dermal sheath is more intense in catagen than in anagen follicles. CD34 immunostaining of the external root sheath was seen in adult anagen follicles but not in fetal follicles. This staining of the anagen outer sheath tends to disappear in catagen and is not detected in telogen.
Conclusions  CD10 and CD34 are not proteins constantly present in a specific cell type of the hair follicle, but are proteins that can be expressed by both epithelial and mesenchymal cells depending on the stage of development and hair cycle. The distribution of the immunoreactivity to CD10 in the placode and CD34 in the dermal condensate suggests a role of these proteins in initial stages of hair formation.     

Effects of interleukins, colony-stimulating factor and tumour necrosis factor on human hair follicle growth in vitro: a possible role for interleukin-1 and tumour necrosis factor-α in alopecia areata

The immune system may be involved in the regulation of normal hair follicle growth as well as in the pathogenesis of some hair diseases. Immunomodulatory cytokines not only act as mediators of immunity and inflammation but also regulate cell proliferation and differentiation and. as such, may play an important part in regulating hair growth. We have investigated the effects of a number of interleukins (IL). colony stimulating factors and tumour necrosis factors (TNF) on hair follicle growth in vitro. Dose-response studies showed that IL-1α. IL-1ß and TNF-o were potent inhibitors of hair follicle growth. The histology of hair follicles maintained with inhibitory doses of IL-1α. IL-1ß and TNF-α showed similar changes in hair follicle morphology, resulting in the formation of dystrophic anagen hair follicles. These changes in histology were characterized by the condensation and distortion of the dermal papilla, marked vacuolation of the hair follicle matrix, abnormal keratinization of the follicle bulb and inner root sheath, disruption of follicular melanocytes and the presence of melanin granules witbin the dermal papilla. Moreover, these changes in hair follicle morphology are similar to those reported in alopecia areata and suggest that IL-1α, IL-1ß and TNF-α may play an important part in the pathophysiology of inflammatory hair disease.     

Syndecan-1 is strongly expressed in the anagen hair follicle outer root sheath and in the dermal papilla but expression diminishes with involution of the hair follicle

Syndecan-1 is the prototypic member of a family of heparan sulfate-bearing cell surface proteoglycans that function in adhesion, cell-extracellular matrix interactions, migration, and proliferation. During embryogenesis, syndecan-1 expression in the epithelium is downregulated when the epithelium gives rise to motile mesenchymal cells, whereas mesenchymal syndecan-1 expression is upregulated during organ formation. In aggressive basal cell carcinomas, syndecan-1 expression is evident in the stroma. Some neoplastic cells induce stroma to meet needs for growth, and it may be the mesenchymal cells that produce and shed syndecan-1 into the stroma. The physiologic mechanism by which the hair follicle undergoes its cyclic process of involution and formation of a new active hair follicle is not well understood. Sixty scalp biopsies and a large scalp resection were evaluated for syndecan-1 expression within hair follicles in the growing (anagen), involuting (catagen), and resting (telogen) phases. Strong syndecan-1 immunoreactivity was evident in the outer root sheath (ORS) of the anagen hair follicle, but this expression diminished in intensity with the involution and resting stages in the hair follicle cycle. The diminution of syndecan-1 immunoreactivity in the ORS of involuting and resting hair follicles may be a result of terminal keratinocyte differentiation. Syndecan-1 was also present in the dermal papilla of the anagen hair follicle, where it may promote growth factor-mediated cell signaling that induces and maintains growth of the hair shaft and the inner root sheath.     

Hair cycle-dependent changes in adrenergic skin innervation, and hair growth modulation by adrenergic drugs

Skin nerves may exert "trophic" functions during hair follicle development, growth, and/or cycling. Here, we demonstrate hair cycle-related plasticity in the sympathetic innervation of skin and hair follicle in C57BL/6 mice. Compared with telogen skin, the number of nerve fibers containing norepinephrine or immunoreactive for tyrosine hydroxylase increased during the early growth phase of the hair cycle (anagen) in dermis and subcutis. The number of these fibers declined again during late anagen. beta2-adrenoreceptor-positive keratinocytes were transiently detectable in the noncycling hair follicle epithelium, especially in the isthmus and bulge region, but only during early anagen. In early anagen skin organ culture, the beta2-adrenoreceptor agonist isoproterenol promoted hair cycle progression from anagen III to anagen IV. The observed hair cycle-dependent changes in adrenergic skin innervation on the one hand, and hair growth modulation by isoproterenol, accompanied by changes in beta2-adrenoreceptor expression of selected regions of the hair follicle epithelium on the other, further support the concept that bi-directional interactions between the hair follicle and its innervation play a part in hair growth control. This invites one to systematically explore the neuropharmacologic manipulation of follicular neuroepithelial interactions as a novel therapeutic strategy for managing hair growth disorders.     

Two- and three-dimensional demonstrations of morphological alterations of early anagen hair follicle with special reference to the bulge area

During late telogen to early anagen secondary hair germ is newly formed by the downgrowth of a clubbed column which is indistinguishable from the bulge. Serial vertical sections demonstrated that the early anagen terminal hair follicle formed the new secondary hair germ associated with a lateral protuberance of basaloid cells which could be considered as the bulge of the new hair follicle. Interestingly, the arrector pili muscle bundle was divided into two branches, one inserted into the original clubbed end and the other into this protuberance of the secondary hair germ. CAM5.2-reactive Merkel cells were present not only in the clubbed ends of the old follicle but also in the protuberance of the new hair germ. The formation of the lateral protuberance of the new hair germ preceded the appearance of CAM5.2-reactive Merkel cells in this location. Ks19.1 immunoreactivity was observed from the clubbed end to the upper half of the new hair germ. These phenomena occurred in early anagen before the club hairs were shed. It is postulated that the early anagen hair follicle formed the area within the new hair germ equivalent to the bulge and Merkel cells either moved from the bulge of the old hair follicle or differentiatedde novo from immature epithelial cells. Merkel cells or their products in the bulge may serve as attractants for the readjusting arrector pili muscle to anchor to the bulge of the new hair follicle.     

Proteoglycan expression patterns in human hair follicle

BACKGROUND: Proteoglycans (PGs) are known to play key roles in many cellular signalling pathways involved in hair follicle biology. Although some PG core proteins have previously been described in adult human hair follicles, their glycosaminoglycan (GAG) moieties have been less studied. OBJECTIVES: To add knowledge about PG core protein and GAG distributions in human anagen hair follicle and, for selected follicles, during catagen. METHODS: We used immunohistochemistry and immunohistofluorescence to revisit the expression pattern of GAG chains and core proteins in human hair follicle. The studied epitopes included CD44v3, syndecan-1, perlecan, versican, aggrecan, biglycan, heparan sulphate (HS), chondroitin sulphate (CS), dermatan sulphate (DS) and keratan sulphate (KS). RESULTS: The membrane PGs syndecan-1 and CD44v3 were respectively detected in the epithelial part of whole hair and in the outer root sheath basal layer. The dermal part of the hair follicle contained high amounts of extracellular PGs such as perlecan, versican, aggrecan, biglycan and their saccharidic moieties, namely HS, CS, DS and KS. We also observed a variable distribution of these components along the hair follicle. Especially, we noted a PG impoverishment at the very bottom of the anagen bulb. Moreover, while type D chondroitin expression remained unaffected, 4C3-CS and PG4-CS/DS epitopes respectively decreased in the dermal papilla and the connective tissue sheath, at the onset of catagen. CONCLUSIONS: GAG and PG expression along the human anagen hair follicle was characterized by (i) discontinuities mainly affecting the basement membrane and (ii) disappearance of some epitopes at catagen onset. These results are discussed in term of functionalities in nutrient diffusion, cell proliferation and differentiation, and hair protection.     

The angiogenic properties of the rat vibrissa hair follicle associate with the bulb

As the hair follicle is one of the most rapidly growing tissues in the body, it must be nourished by a rich blood supply. Histological studies have indicated that the number of vessels about a growing follicle exceeds that about a resting follicle, so we postulated that the hair follicle might provide its own angiogenic stimulus during certain phases of its growth. Reported here are experiments testing the angiogenic properties of the growing (anagen) hair follicle. Using the rabbit corneal pocket angiogenesis assay and cycled anagen rat vibrissae hair follicles, we found that the mesenchymal dermal papilla had no angiogenic properties, but the anagen bulb was angiogenic. These findings suggest a mechanism for the cycling of hair follicles and an example of normal epithelium to mesenchyme interactions.