In a world first, a University of Melbourne study has shown that topical estrogen could help prevent HIV infection by blocking entry of the virus into the human penis.

[editor's note] (Andrew): The only reason I’m not scrubbing this trash study off my website is to mock it.

But good news for readers, because I’m awarding a Think Gene coffee mug to the first reader who forwards me a spam email hawking topical oestrogen as an “all natural” penis cream to “u last longr.”

The study to be published in PLoS ONE journal today reveals that application of estrogen to the human penis increased the thickness of the natural keratin layer on the skin, which could prevent HIV from infecting the male.

The epithelium of the human penis is richly supplied with estrogen receptors suggesting it could respond to topical estrogen.

Dr Andrew Pask from the Department of Zoology at the University of Melbourne analyzed the tissue samples from 12 foreskins and made the discovery.

“This suggested that estrogen could induce a thickening of the keratin layer of the foreskin epidermis in the same way as it acts in the vagina,” said Dr Pask.

“Keratin on our skin acts a barrier to viral infection. We hope to be able to enhance this protection with the use of a naturally occurring, weak estrogen,” said Professor Roger Short of the Faculty of Medicine, Dentistry and Health Sciences who lead the research.

To confirm its effect, topical estrogen was applied to the human foreskin for a two week trial. This resulted in a rapid and substantial increase in keratin thickness.

“We have found a new avenue to possibly prevent HIV infection of the penis.”

HIV is one of the greatest health crises the world has ever seen, and affects over 40 million people worldwide.

Source: The University of Melbourne

Kevin: HIV is on the rise around the world and a treatment such as this could have impact where condoms are not socially acceptable because of adverse societal influence. Estrogen on the penis would be fine, and while it’s nothing like condoms for preventing HIV (and anti-retrovirals at your local free HIV drug stand) this could mean something in terms of harm reduction.

Pask AJ, McInnes KJ, Webb DR, Short RV (2008) Topical Oestrogen Keratinises The Human Foreskin and May Help Prevent HIV Infection. PLoS ONE 3(6): e2308. doi:10.1371/journal.pone.0002308

Using a breakthrough technology, researchers led by a Weill Cornell Medical College scientist have pinpointed the hormone estrogen as a key player in about half of all prostate cancers.

Estrogen-linked signaling helps drive a discrete and aggressive form of the disease caused by a chromosomal translocation, which in turn results in the fusion of two genes.

“Fifty percent of prostate cancers harbor a common recurrent gene fusion, and we believe that this confers a more aggressive nature to these tumors,” explains study senior author Dr. Mark A. Rubin, professor of pathology and laboratory medicine, and vice chair for experimental pathology at Weill Cornell Medical College. Dr. Rubin is also attending pathologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

“Interfering with this gene fusion — or its downstream molecular pathways — will be crucial in the search for drugs that fight the disease. Based on our new data, we now believe that inhibiting estrogen may be one way of doing so,” he says.

The findings are published in the May 27 online edition of the Journal of the National Cancer Institute. Dr. Rubin conducted the study while at the Brigham and Women’s Hospital and in collaboration with Dr. Todd Golub and other members of the Broad Institute of MIT and Harvard, in Cambridge, Mass. His team is now continuing this line of research at Weill Cornell.

Dr. Rubin, along with researchers at the University of Michigan, first discovered and described the common fusions between the TMPRSS2 and ETS family member genes subset of prostate cancer in the journal Science in 2005. “The discovery showed that these malignancies occur after an androgen (male hormone)-dependent gene fuses with an oncogene — a type of gene that causes cancer,” he explains.

Experts have long understood that male hormones help spur prostate cancer — in fact, androgen-deprivation therapy is a first-line treatment against the disease. And yet the disease can progress despite androgen reduction, suggesting that other pathways might be at work.

“So, we wanted to learn more — what is the genetic and molecular ‘fingerprint’ of this aggressive subset of prostate tumor”" Dr. Rubin says.

Answering that question required the analysis of 455 prostate cancer samples from trials in Sweden and the United States that were conducted as far back as the mid-1970s.

“These samples were placed in fixative and not frozen, so we needed new methods of retrieving the genetic information,” Dr. Rubin says. To do so, his team led by co-lead authors Dr. Sunita Setlur and Dr. Kirsten Mertz developed an innovative technology for effectively “reading” the gene transcription profiles hidden in the samples.

“That led us to perform the largest gene-expression microarray analysis yet conducted in prostate cancer research, amassing information on more than 6,000 genes,” Dr. Rubin says. “This allowed us to obtain a robust, 87-gene expression ’signature’ that distinguishes fusion-positive TMPRSS2-ERG cancers from other prostate malignancies.”

A close analysis of the signature yielded a surprise: that estrogen-dependent molecular pathways appear to play a crucial role in regulating (and encouraging) this aggressive subset of prostate cancer.

While estrogen is typically thought of as a “female” hormone, men produce it as well.

“Now, we show for the first time that this natural estrogen can stimulate the production of the cancer-linked TMPRSS2-ERG transcript, via the estrogen receptor (ER)-alpha and ER-beta. These receptors are found on the surface of some prostate cancer cells,” Dr. Rubin explains.

The finding could have implications for prostate cancer research, including drug development. According to Dr. Rubin, “We now believe that agents that dampen estrogen activity (ER-beta antagonists) could inhibit fusion-positive prostate cancers. Alternatively, any intervention that boosts estrogen activity (ER-alpha) might also give a boost to these aggressive malignancies.”

Research into just why fusion-positive prostate cancers are so aggressive — and potential molecular drug targets to help curb that aggression — will continue under Dr. Rubin’s direction at Weill Cornell, in collaboration with members of his group and with computational biologist Dr. Francesca Demichelis.

“The technological achievement of using fixed samples that were up to 30 years old is significant,” Dr. Rubin says. “In the future, we hope to explore banked tissues from clinical trials to help understand why they failed. This should lead to insight for designing the next trial.”

Source: New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College

Sunita R. Setlur, Kirsten D. Mertz, Yujin Hoshida, Francesca Demichelis, Mathieu Lupien, Sven Perner, Andrea Sboner, Yudi Pawitan, Ove Andrén, Laura A. Johnson, Jeff Tang, Hans-Olov Adami, Stefano Calza, Arul M. Chinnaiyan, Daniel Rhodes, Scott Tomlins, Katja Fall, Lorelei A. Mucci, Philip W. Kantoff, Meir J. Stampfer, Swen-Olof Andersson, Eberhard Varenhorst, Jan-Erik Johansson, Myles Brown, Todd R. Golub, and Mark A. Rubin. Estrogen-Dependent Signaling in a Molecularly Distinct Subclass of Aggressive Prostate Cancer. Journal of the National Cancer Institute Advance Access published on May 27, 2008. doi:10.1093/jnci/djn150

Josh says:

This has a lot of potential to help prostate cancer patients. Knowing that we should also try to inhibit estrogen and estrogen production in these patients is a novel strategy and hopefully will help save a lot of lives.