Androgen receptor-mediated inhibition of cutaneous wound healing
Androgen receptor-mediated inhibition of cutaneous wound healing
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DOI：
10.1172/jci200215704
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发表时间：
2002-09-01
影响因子：
15.9
通讯作者：
Mills, SJ
中科院分区：
文献类型：
--
作者：
Ashcroft, GS;Mills, SJ
老年人伤口愈合状态受损会导致相当大的发病率和死亡率，并每年给美国卫生服务造成超过90亿美元的成本。除了固有的衰老本身导致愈合延迟外，研究表明在伤口修复方面存在显著的性别差异。我们报告说，去势雄性小鼠可以显著加速局部皮肤伤口的愈合，并与炎症反应减少和毛发生长增加有关。使用无毛小鼠模型，我们已经证明，睾酮的减少不是通过毛囊上皮/间充质细胞的增殖来刺激愈合反应，而是直接通过对伤口细胞群的影响来刺激愈合反应。我们认为，内源性睾丸素抑制男性皮肤伤口愈合反应，并与增强的炎症反应有关。观察到的效应背后的机制涉及到巨噬细胞对睾酮的反应直接上调了促炎细胞因子的表达。通过受体拮抗，系统地阻断雄激素的作用，显著加速愈合，这表明未来治疗老年男性创面愈合受损状态的干预是一个特定的靶点。
Impaired wound healing states in the elderly lead to substantial morbidity, mortality, and a cost to the US Health Services of over $9 billion per annum. In addition to intrinsic aging per se causing delayed healing, studies have suggested marked sex-differences in wound repair. We report that castration of male mice results in a striking acceleration of local cutaneous wound healing, and is associated with a reduced inflammatory response and increased hair growth. Using a hairless mouse model, we have demonstrated that testosterone reduction stimulates the healing response not through hair follicle epithelial/mesenchymal cell proliferation, but directly via effects on wound cell populations. We suggest that endogenous testosterone inhibits the cutaneous wound healing response in males and is associated with an enhanced inflammatory response. The mechanisms underlying the observed effects involve a direct upregulation of proinflammatory cytokine expression by macrophages in response to testosterone. Blockade of androgen action systemically, via receptor antagonism, accelerates healing significantly, suggesting a specific target for future therapeutic intervention in impaired wound healing states in elderly males.