Androgen receptor co-activator Hic-5/ARA55 as a molecular regulator of androgen sensitivity in dermal papilla cells of human hair follicles
Androgen receptor co-activator Hic-5/ARA55 as a molecular regulator of androgen sensitivity in dermal papilla cells of human hair follicles
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DOI：
10.1038/sj.jid.5700883
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发表时间：
2007-10-01
影响因子：
6.5
通讯作者：
Itami, Satoshi
中科院分区：
文献类型：
--
作者：
Inui, Shigeki;Fukuzato, Yoko;Itami, Satoshi
雄激素部位-通过毛乳头中的雄激素受体特异性地影响青春期后人类头发的生长，雄激素受体与辅助激活剂一起反式激活目标基因。为了研究雄激素对毛囊敏感性的调节，我们重点研究了雄激素受体共激活剂Hic-5/ARA55。哺乳动物双杂交实验证实了其与胡须毛乳头细胞雄激素受体的相互作用。半定量逆转录-聚合酶链式反应显示，Hic-5/ARA55mRNA在胡须和秃头皮毛乳头细胞中高表达，在枕头皮毛乳头细胞中低表达。为确定Hic-5/ARA55mRNA水平是否与其内源性活性相关，我们采用小鼠乳腺肿瘤病毒荧光素酶方法研究了显性阴性Hic-5/ARA55对R1881诱导的雄激素受体反式激活的影响。我们发现，它对胡须和秃头皮毛乳头细胞的反式激活抑制率分别为64.5%和71.4%，而对枕部头皮细胞的反式激活作用不明显。我们的研究结果表明，Hic-5/ARA55是人毛囊雄激素敏感性的分子调节因子。
Androgen site- specifically affects human hair growth after puberty through androgen receptors in the dermal papilla, which transactivate target genes acting in conjunction with co- activators. To examine the regulation of androgen sensitivity in hair follicles, we focused on androgen receptor co- activator Hic- 5/ ARA55. Its interaction with transfected androgen receptor in beard dermal papilla cells was confirmed with mammalian two- hybrid assays. The semiquantitative reverse transcriptase- polymerase chain reaction showed that Hic- 5/ ARA55 mRNA expression was high in dermal papilla cells from the beard and bald frontal scalp but low in cells from the occipital scalp. To determine whether Hic- 5/ ARA55 mRNA level correlates with its endogenous activity, we studied the effect of dominant negative Hic- 5/ ARA55 on transfected androgen receptor transactivation induced by R1881 using mouse mammary tumor virus- luciferase assays. We found that it suppressed the transactivation by 64.5 and 71.4% in dermal papilla cells from the beard and bald frontal scalp, respectively, whereas it showed no significant effect in cells from the occipital scalp. Our findings suggest that Hic- 5/ ARA55 is a molecular regulator for androgen sensitivity in human hair follicles.