Phosphodiesterase 11 (PDE11): is it a player in human testicular function?

PDE11, the newest member of the PDE family of phosphodiesterases, has become the center of controversy. Four splice variants were recently identified, PDE11A1-4. Historical data have suggested that PDE11A3 is found in the testis while PDE11A4 is found in the prostate. The controversial issue is the inhibition of PDE11 by tadalafil. In the light of tadalafil's commercial success, its inhibition of PDE11A has been the subject of heated debate. A variety of published reports addressed this issue, suggesting that the target organ of tadalafil's inhibition, the testis, is not adversely affected. Daily tadalafil given to healthy volunteers did not alter semen analysis parameters or blood hormonal parameters, seemingly mitigating the clinical effect of the PDE11 inhibition. However, two recent papers published in this journal have added fuel to this proverbial fire. In this perspective, Sharron Francis, a noted PDE expert, and a co-author of one of the recent papers mentioned above, sheds further light on this contested topic.