Studies shed light on mechanism behind erections, ED

October 3, 2012

Two recent studies shed new light on the mechanism of maintaining an erection and genetic markers linked to erectile dysfunction after radiation therapy.

Two recent studies shed new light on the mechanism of maintaining an erection and genetic markers linked to erectile dysfunction after radiation therapy.

In a mouse model, researchers from several institutions found a complex positive feedback loop in the penile nerves that triggers waves of nitric oxide to keep the penis erect. After the initial release of nitric oxide, phosphorylation takes place to continue its release and sustain the erection, researchers say.

“We’ve closed a gap in our knowledge. Now… we know that nitric oxide is not just a blip here or there, but instead it initiates a cyclic system that continues to produce waves of the neurotransmitter from the penile nerves,” said senior author Arthur Burnett, MD, of Johns Hopkins Medicine, Baltimore.

With this basic biologic information, it may be possible to develop new medical approaches to help men with erection problems caused by such factors as diabetes, vascular disease, or nerve damage from surgical procedures, according to Dr. Burnett. Such new approaches could be used to intervene earlier in the arousal process than current medicines approved to treat ED.

In particular, Dr. Burnett said, "The target for new therapies would be the protein kinase A (PKA) phosphorylation of neuronal nitric oxide synthase (nNOS). Now that we know the mechanism for causing the 'activated' form of nNOS in penile nerves, we can develop agents that exploit this mechanism to help with erection difficulties."

Results from the study were published online in Proceedings of the National Academy of Sciences (Sept. 24, 2012).

Separately, results of a multicenter study uncovered 12 genetic markers associated with the development of ED in prostate cancer patients who were treated with radiation.

In the large-scale, genome-wide association study, the researchers sought first to discover the candidate genetic markers of side effect risk, and second, to confirm which of those markers are replicated in a second group of patients. In the first group of prostate cancer patients, which included 132 men who developed ED after radiotherapy and 103 men similarly treated who did not develop ED, they found a set of genetic markers associated with ED. In the second part of the study, which examined 128 patients who developed ED after radiotherapy and 102 who did not, the investigators confirmed that 12 single nucleotide polymorphisms were associated with ED.

"The risk of developing erectile dysfunction after radiation treatment is highly variable, suggesting there may be a genetic component to determining that risk. Our study confirms that specific markers make certain patients more susceptible to this side effect," said senior author Barry Rosenstein, PhD, of Mount Sinai School of Medicine, New York.

Results from the study were published online in the International Journal of Radiation Oncology • Biology • Physics (Sept. 26, 2012).

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