Topical Oestrogen Keratinises The Human Foreskin and May Help Prevent HIV Infection
Topical Oestrogen Keratinises The Human Foreskin and May Help Prevent HIV Infection
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DOI：
10.1371/journal.pone.0002308
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发表时间：
2008-06-04
期刊：
影响因子：
3.7
通讯作者：
Short, Roger V.
中科院分区：
文献类型：
--
作者：
Pask, Andrew J.;McInnes, Kerry J.;Short, Roger V.
随着艾滋病毒发病率的不断上升，迫切需要开发简单、廉价且有效的预防艾滋病毒感染的新方法。男性包皮环切术可将感染风险降低约 60%，这可能是因为去除了包皮内大量的朗格汉斯细胞，而朗格汉斯细胞是 HIV 进入阴茎的主要途径。朗格汉斯细胞是人体天然防御艾滋病毒的重要组成部分，只有当它们暴露于高水平的艾滋病毒病毒体时才会引起感染。与其通过包皮环切术消除这种自然防御机制，不如通过增厚朗格汉斯细胞上的角蛋白层来增强它，从而减少它们所暴露的病毒载量。我们研究了局部施用雌激素诱导内包皮上皮角化的能力。从组织化学角度来看，整个包皮富含雌激素受体。内包皮的上皮与阴道一样，在 24 小时内通过角化对局部施用雌三醇产生反应，并且在治疗停止后该反应持续至少 5 天。雌三醇是一种廉价、容易获得的天然雌激素代谢物，可迅速使内包皮（艾滋病毒进入阴茎的部位）角化。角蛋白保护层的增厚应该会减少下面的朗格汉斯细胞对 HIV 病毒体的暴露。这种简单的治疗方法可以成为包皮环切术的辅助或替代方法，以减少男性艾滋病毒感染的发生率。
With the growing incidence of HIV, there is a desperate need to develop simple, cheap and effective new ways of preventing HIV infection. Male circumcision reduces the risk of infection by about 60%, probably because of the removal of the Langerhans cells which are abundant in the inner foreskin and are the primary route by which HIV enters the penis. Langerhans cells form a vital part of the body's natural defence against HIV and only cause infection when they are exposed to high levels of HIV virions. Rather than removing this natural defence mechanism by circumcision, it may be better to enhance it by thickening the layer of keratin overlying the Langerhans cells, thereby reducing the viral load to which they are exposed. We have investigated the ability of topically administered oestrogen to induce keratinization of the epithelium of the inner foreskin. Histochemically, the whole of the foreskin is richly supplied with oestrogen receptors. The epithelium of the inner foreskin, like the vagina, responds within 24 hours to the topical administration of oestriol by keratinization, and the response persists for at least 5 days after the cessation of the treatment. Oestriol, a cheap, readily available natural oestrogen metabolite, rapidly keratinizes the inner foreskin, the site of HIV entry into the penis. This thickening of the overlying protective layer of keratin should reduce the exposure of the underlying Langerhans cells to HIV virions. This simple treatment could become an adjunct or alternative to surgical circumcision for reducing the incidence of HIV infection in men.