This Article Full Text Full Text (PDF) All Versions of this Article: 29/1/3    most recent Author Manuscript (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Burnett, A. L. Search for Related Content PubMed PubMed Citation Articles by Burnett, A. L.

Review

Molecular Pharmacotherapeutic Targeting of PDE5 for Preservation of Penile Health

From the Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Johns Hopkins University School of Medicine, Baltimore, Maryland.

Correspondence to: Dr Arthur L. Burnett, Department of Urology, Johns Hopkins Hospital, 600 N. Wolfe St/Marburg 407, Baltimore, MD 21287-2411 (e-mail: aburnett{at}jhmi.edu).

Abstract

The molecular science of erection physiology has established that phosphodiesterase 5 (PDE5) serves an important biological role in the penis. Current research in the field has revealed this molecular effector to be relevant for penile erection, controlling the erectile response by degrading the second messenger product of the erection mediatory nitric oxide (NO) signaling pathway, 3', 5'-cyclic guanosine monophosphate. Accordingly, PDE5 has been targeted for sexual medicine purposes, and orally administered PDE5 inhibitors such as sildenafil, tadalafil, and vardenafil comprise a foremost intervention for erectile dysfunction (ED). New investigation of PDE5 regulation in the penis has suggested alternative roles for the enzyme and new therapeutic opportunities involving its molecular interactions. In particular, PDE5 function is altered under derangements of androgen deficiency, decreased NO bioactivity, and oxidative stress-associated inflammatory changes, thus contributing to an assortment of erectile disorders including hypogonadism-associated ED, recurrent ischemic priapism, penile vasculopathy, and penile fibrosis. This review provides a critical examination of the multifaceted role of the PDE5 regulatory system in the penis and its relevance for applying existing and emerging therapeutic strategies for erectile disorders.