Mechanism of action of androgen in human hair follicles

细胞内信号转导的一个典型例子是雄激素-雄激素受体系统。雄激素受体作为配体依赖性转录因子，在人毛发周期调控中起着重要作用。胡须和腋窝真皮乳头细胞（DPC）强烈表达雄激素受体mRNA。I型5α-还原酶基因的表达是DPC的普遍特征，而II型5α-还原酶基因的表达仅限于颊DPC。ⅱ型17β-羟基类固醇脱氢（HSD） mRNA在根外鞘细胞中强烈表达，而除雄性腋毛外，DPCs不表达ⅱ型17β-HSD mRNA。相比之下，III型17β-HSD mRNA在两种性别的胡须DPCs和腋窝DPCs中均有强烈表达，ORSCs表达水平较低。DPCs中ⅲ型17β-HSD mRNA的表达不受雄激素的调控。这些结果表明，毛发对雄激素的敏感性部分受AR、5α-还原酶和17β-HSD在DPCs中的位点特异性表达控制。通过转基因小鼠模型实验发现，EGF受体信号在诱导原诱导中起重要作用。Stat3是细胞因子的下游信号分子，包括EGF和HGF。Stat3的条件基因靶向在小鼠中显示严重损害毛发周期和伤口愈合过程。生长因子依赖的stat3破坏的角质形成细胞的体外迁移受到损害，尽管有正常的增殖反应。Stat3在皮肤重塑，即新生细胞诱导和伤口愈合中起着至关重要的作用。

One of the typical example of the signal transduction in the cell is androgen-androgen receptor system. Androgen receptor, ligand dependent transcription factor, is apparently involved in hair cycle control in hunman. Beard and axillary dermal papilla cells (DPC) strongly expressed androgen receptor mRNA. While the expression of type I 5α-reductase is ubiquitous property of DPC, type II 5α-reductase gene expression is limited to beard DPC. Type II 17β-hydroxysteroid dehydrogenas (HSD) mRNA was strongly expressed in outer root sheath cells, while DPCs except for male axillary hair expressed no type II 17β-HSD mRNA. In contrast, type III 17β-HSD mRNA was strongly expressed in beard DPCs and axillary DPCs from both sexes, ORSCs showed a low level of expression.Expression of type III 17β-HSD mRNA was not regulated by androgen in DPCs. These results suggest that the sensitivity of hairs to androgen is partially controlled by the site specific expression of AR, 5α-reductase and 17β-HSD in DPCs.EGF receptor signaling has been found to play an important role in catagen induction by the experiments of transgenic mouse models. Stat3 is a down stream signaling molecule of cytokines, growth factors including EGF and HGF. Conditional gene targeting of Stat3 in mice showed severely compromised hair cycle and wound healing processes. Growth factor-dependent in vitro migration of the Stat3-disrupted keratinocytes was impaired despite normal proliferative responses. Stat3 plays a crucial role in skin remodeling, that is, anagen induction and wound healing.