雄激素性脱发的分子基础:通过毛乳头从雄激素到旁分泌介质。

PubMed ID
G H
发表日期 2011年Jan月

原始出处 皮肤科学杂志
Journal of dermatological science
作者 Inui  Shigeki  Itami  Satoshi 

文献标题 雄激素性脱发的分子基础:通过毛乳头从雄激素到旁分泌介质。
Molecular basis of androgenetic alopecia: From androgen to paracrine mediators through dermal papilla.
Molecular basis of androgenetic alopecia: From androgen to paracrine mediators through dermal papilla.

文献摘要

雄激素性脱发(AGA)的特征是头皮毛发发生天鹅绒样改变,在毛发生长期缩短的重复周期中,毛囊缩小。这种现象主要由雄激素介导。雄激素的多步分子途径可能参与AGA的发病机制。Ⅱ型5α-还原酶在AGA和beard毛乳头细胞中的表达高于其它部位。另一方面,I型5α-还原酶的表达相对较低。其次,激素结合实验和RT-PCR证实雄激素受体(AR)在秃发毛乳头细胞中的表达显著高于非秃发毛乳头细胞。此外,雄激素敏感部位(如AGA和beard)的毛囊毛乳头细胞中,AR共激活因子Hic-5/ARA55高表达。总之,Ⅱ型5α-还原酶、AR和Hic-5/ARA55的表达增强可上调AGA毛乳头细胞对雄激素的敏感性。此外,在AR过表达的人AGA毛乳头细胞与正常人角质形成细胞的共培养中,R1881通过雄激素诱导的TGF-β1抑制角质形成细胞的生长,表明TGF-β1是AGA发病的关键因素之一。TGF-β2和DKK-1是雄激素诱导的卵泡上皮细胞生长抑制因子。我们期望将来能发现更多的致病介质,使我们更容易理解AGA的发病机制,并从男科角度提供新的治疗靶点。


Androgenetic alopecia (AGA) is characterized by vellus transformation of scalp hairs, corresponding to hair follicle miniaturization during repeated hair cycles with shortened anagen phase. This phenomenon is mediated mainly by androgen. Then, the multi-step molecular pathway of androgen can be involved in the pathogenesis of AGA. The expression of type II 5α-reductase is higher in dermal papilla cells from AGA and beard than those from other sites. On the other hand, type I 5α-reductase expression is relatively low. Next, hormone binding assays and RT-PCR demonstrated that androgen receptor (AR) expression is significantly higher in bald dermal papilla cells than non-bald cells. Additionally, AR coactivator Hic-5/ARA55 is highly expressed in dermal papilla cells of hair follicles from androgen-sensitive sites such as AGA and beard. Collectively, the enhanced expression of type II 5α-reductase, AR and Hic-5/ARA55 can upregulate sensitivity to androgen of dermal papilla cells in AGA. Furthermore, in the coculture of AR-overexpressing human dermal papilla cells from AGA and normal human keratinocytes, R1881 suppresses keratinocyte growth through androgen-inducible TGF-β1, indicating that TGF-β1 is one of the key players in pathogenesis of AGA. TGF-β2 and DKK-1 has been reported to be androgen-induced suppressor of growth of follicular epithelial cells. We expect that more pathogenic mediators will be identified in the future, enabling easier understanding of AGA pathogenesis and providing new therapeutic targets from aspect of andrology.

Androgenetic alopecia (AGA) is characterized by vellus transformation of scalp hairs, corresponding to hair follicle miniaturization during repeated hair cycles with shortened anagen phase. This phenomenon is mediated mainly by androgen. Then, the multi-step molecular pathway of androgen can be involved in the pathogenesis of AGA. The expression of type II 5α-reductase is higher in dermal papilla cells from AGA and beard than those from other sites. On the other hand, type I 5α-reductase expression is relatively low. Next, hormone binding assays and RT-PCR demonstrated that androgen receptor (AR) expression is significantly higher in bald dermal papilla cells than non-bald cells. Additionally, AR coactivator Hic-5/ARA55 is highly expressed in dermal papilla cells of hair follicles from androgen-sensitive sites such as AGA and beard. Collectively, the enhanced expression of type II 5α-reductase, AR and Hic-5/ARA55 can upregulate sensitivity to androgen of dermal papilla cells in AGA. Furthermore, in the coculture of AR-overexpressing human dermal papilla cells from AGA and normal human keratinocytes, R1881 suppresses keratinocyte growth through androgen-inducible TGF-β1, indicating that TGF-β1 is one of the key players in pathogenesis of AGA. TGF-β2 and DKK-1 has been reported to be androgen-induced suppressor of growth of follicular epithelial cells. We expect that more pathogenic mediators will be identified in the future, enabling easier understanding of AGA pathogenesis and providing new therapeutic targets from aspect of andrology.


获取全文 10.1016/j.jdermsci.2010.10.015