5α-Dihydrotestosterone (DHT) retards wound closure by inhibiting re-epithelialization
5α-Dihydrotestosterone (DHT) retards wound closure by inhibiting re-epithelialization
复制标题
DOI：
10.1002/path.2444
复制
发表时间：
2009-01-01
影响因子：
7.3
通讯作者：
Ashcroft, G. S.
中科院分区：
文献类型：
--
作者：
Gilliver, S. C.;Ruckshanthi, J. P. D.;Ashcroft, G. S.
正在进行的研究，以解释为什么老年男性愈合急性皮肤伤口比他们的女性同行更慢（和更强烈地倾向于慢性溃疡的条件）已确定内源性雌激素和雄激素分别作为修复的增强剂和抑制剂。我们以前证明，阻断睾酮转化为5 α-二氢睾酮（DHT）限制了其损害愈合的能力，这表明DHT是一种比睾酮更有效的修复抑制剂。本研究旨在阐明雄激素延迟修复的中枢机制。虽然大鼠体内伤口和体外成纤维细胞浸渍的胶原盘的收缩特性似乎都不受雄激素操作的影响，但DHT生物合成的整体阻断显著加速了切口和切除伤口的上皮再形成，并降低了β-连环蛋白（修复的关键抑制剂）的局部表达。此外，双氢睾酮延缓表皮角质形成细胞在体外迁移的划痕伤。相比之下，它未能影响真皮成纤维细胞的迁移和增殖特性，表明其主要抑制作用是在再上皮化后。这些新的发现可能在慢性溃疡的背景下特别重要，男性是一个关键的风险因素。版权所有（C）2008大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
The ongoing search for explanations as to why elderly males heal acute skin wounds more slowly than do their female counterparts (and are more strongly disposed to conditions of chronic ulceration) has identified endogenous oestrogens and androgens as being respectively enhancers and inhibitors of repair. We previously demonstrated that blocking the conversion of testosterone to 5 alpha-dihydrotestosterone (DHT) limits its ability to impair healing, suggesting that DHT is a more potent inhibitor of repair than is testosterone. The present study aimed to delineate the central mechanisms by which androgens delay repair. Whilst the contractile properties of neither rat wounds in vivo nor fibroblast-impregnated collagenous discs in vitro appeared to be influenced by androgen manipulations, the global blockade of DHT biosynthesis markedly accelerated re-epithelialization of incisional and excisional wounds and reduced local expression of beta-catenin, a key inhibitor of repair. Moreover, DHT retarded the in vitro migration of epidermal keratinocytes following scratch wounding. By contrast, it failed to influence the migratory and proliferative properties of dermal fibroblasts, suggesting that its primary inhibitory effect is upon re-epithelialization. These novel findings may be of particular significance in the context of chronic ulceration, for which being male is a key risk factor. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.