Abstract
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.
Highlights
In 2006, 39.5 million people were currently infected with HIV, and there were 4.3 million new infections, making HIV one of the greatest health crises in human history
We have examined the ability of topical oestrogen to increase keratin production by the inner foreskin epithelium
In order to determine if the inner foreskin could respond to topical oestriol, we examined the mRNA expression and protein distribution of the two oestrogen receptors (ER) ERa and ERb, in the foreskins of six adult men aged 30–65, undergoing elective surgical circumcisions. mRNA transcripts for both ERa and ERb were detected in samples taken from the inner and outer foreskin (Figure S1)
Summary
In 2006, 39.5 million people were currently infected with HIV, and there were 4.3 million new infections, making HIV one of the greatest health crises in human history. The results of three large randomised trials of male circumcision, carried out in South Africa [1], Kenya [2] and Uganda [3], leave no doubt that circumcision more than halves a man’s risk of HIV infection [4,5], and the protective effect is thought to be due to the physical removal of most of the inner foreskin epithelium. This epithelium is richly supplied with Langerhans cells, the main site of HIV entry into the penis [6]. When large amounts of virus are present, the Langerin reserves may be depleted, so that the Langerhans cells instead become vectors for transporting virus to the regional lymph nodes, establishing a systemic infection
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