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Mechanism of action of androgen in human hair follicles

雄激素在人毛囊中的作用机制

基本信息

批准号：
10670787
负责人：
ITAMI Satoshi
金额：
$ 2.05万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670787/
关键词：
Hair cycle Dermal papilla cells Androgen 5α-reductase Androgen receptor 17β-HSD Growth factor STAT3 5α-reductase 17β-HSD 毛 5alpha-reductase

项目摘要

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.

雄激素-雄激素受体系统是细胞内信号转导的典型例子之一。雄激素受体是一种配体依赖的转录因子，明显参与人类毛发周期的调控。胡须和腋毛乳头细胞(DPC)强表达雄激素受体mRNA。虽然I5型α-还原酶的表达是牙周病的普遍特征，但II型5α-还原酶基因的表达仅限于胡须牙周病。外根鞘细胞表达II型17-羟基类固醇脱氢酶(β-HSDmRNA)，而除男性腋毛外的DPC不表达β-HSDmRNA。与之相反，III17型β-HSD基因在雌雄同体的胡须和腋窝DPC中高表达，ORSCs低水平表达，DPC中III17型β-HSD基因的表达不受雄激素的调节。这些结果表明，毛发对雄激素的敏感性部分受控于DPC中AR、5α还原酶和17β-HSD的位点特异性表达。通过转基因小鼠模型的实验，发现EGF受体信号转导在退变诱导中起重要作用。STAT3是一种细胞因子的下游信号分子，生长因子包括EGF和HGF。STAT3的条件性基因打靶在小鼠身上显示出严重的毛发周期和伤口愈合过程。STAT3破坏的角质形成细胞依赖生长因子的体外迁移受到损害，尽管增殖反应正常。STAT3在皮肤重塑，即生长期诱导和创面愈合中起着至关重要的作用。