Liu Shicheng, Yamauchi Hitoshi
Research Department, Saitama Daiichi Pharmaceutical Co., Ltd., 8-1, Minamisakae-cho, Kasukabe, Saitama 344-0057, Japan.
Biochem Biophys Res Commun. 2008 Apr 18;368(4):858-64. doi: 10.1016/j.bbrc.2008.01.130. Epub 2008 Feb 5.
Androgens regulate hair growth, and 5alpha-reductase (5alphaR) plays a pivotal role in the action of androgens on target organs. To clarify the molecular mechanisms responsible for controlling hair growth, the present study presents evidence that the human follicular dermal papilla cells (DPCs) from either beard (bDPCs) or scalp hair (sDPCs) possess endogenous 5alphaR activity. Real-time RT-PCR revealed that the highest level of 5alphaR1 mRNA was found in bDPCs, followed by sDPCs, and a low but detectable level of 5alphaR1 mRNA was observed in fibroblasts. Minimally detectable levels of 5alphaR2 mRNA were found in all three cell types. A weak band at 26kDa corresponding to the human 5alphaR1 protein was detected by Western blot in both DPCs, but not in fibroblasts. Immuonofluorescence analysis confirmed that 5alphaR1 was localized to the cytoplasm rather than in the nuclei in both DPCs Furthermore, a 5alphaR assay using [(14)C]testosterone labeling in intact cells revealed that testosterone was transformed primarily into androstenedione, and in small amounts, into DHT. Our results demonstrate that the 5alphaR activities of either bDPCs or sDPCs are stronger than that of dermal fibroblasts, despite the fact that the major steroidogenic activity is attributed to 17beta-HSD rather than 5alphaR among the three cell types. The 5alphaR1 inhibitor MK386 exhibited a more potent inhibitory effect on 5alphaR activity than finasteride (5alphaR2 inhibitor) in bDPCs.
雄激素调节毛发生长,5α-还原酶(5αR)在雄激素对靶器官的作用中起关键作用。为阐明控制毛发生长的分子机制,本研究提供证据表明,来自胡须(bDPCs)或头皮毛发(sDPCs)的人毛囊真皮乳头细胞(DPCs)具有内源性5αR活性。实时RT-PCR显示,bDPCs中5αR1 mRNA水平最高,其次是sDPCs,在成纤维细胞中观察到低但可检测水平的5αR1 mRNA。在所有三种细胞类型中均发现最低可检测水平的5αR2 mRNA。通过蛋白质印迹在两种DPCs中均检测到与人类5αR1蛋白相对应的26kDa处的弱条带,但在成纤维细胞中未检测到。免疫荧光分析证实,5αR1在两种DPCs中均定位于细胞质而非细胞核。此外,在完整细胞中使用[(14)C]睾酮标记的5αR测定显示,睾酮主要转化为雄烯二酮,少量转化为双氢睾酮。我们的结果表明,尽管在这三种细胞类型中主要的类固醇生成活性归因于17β-羟类固醇脱氢酶而非5αR,但bDPCs或sDPCs的5αR活性均强于真皮成纤维细胞。5αR1抑制剂MK386在bDPCs中对5αR活性的抑制作用比非那雄胺(5αR2抑制剂)更强。