Basic and Translational Science Lobe-specific Expression of Phosphodiesterase 5 in Rat Prostate Lin Wang, Xiaoyu Zhang, Guifang Wang, Sandhya S. Visweswariah, Guiting Lin, Zhongcheng Xin, Tom F. Lue, and Ching-Shwun Lin OBJECTIVE To investigate the level and location of phosphodiesterase 5 (PDE5) expression in rat prostate. METHODS The ventral, dorsal, and lateral lobes of rat prostate were examined for PDE5 expression by Western blotting. Intact rat urogenital complex, including the urinary bladder and accessory reproductive glands, was examined for PDE5 expression by immunohistochemistry. Individual prostatic lobes were further examined by immunofluorescence for expression of PDE5, a-smooth muscle actin, and rat endothelial cell antigen. RESULTS Western blot analysis showed that PDE5 was expressed at a significantly lower level in dorsal lobe (DL) than in ventral lobe (VL) or lateral lobe (LL). Immunohistochemistry and immunofluo- rescence analyses showed that PDE5 was expressed in both acinar epithelium and periacinar smooth muscle. However, although similar levels of smooth muscle PDE5 expression were observed in all 3 prostatic lobes, significantly lower level of epithelial PDE5 expression was found in DL compared with VL or LL. In prostatic blood vessels, PDE5 expression was clearly visible in the endothelium but not as easily detectable in the smooth muscle. CONCLUSION PDE5 was expressed in the acinar epithelium and periacinar smooth muscle of rat prostate. However, the epithelial PDE5 expression was significantly less in DL than in VL or LL. Regardless, the acinar wall, not the blood vessel wall, is the predominant PDE5 expression site in rat prostate. UROLOGY 85: 703.e7e703.e13, 2015. Ó 2015 Elsevier Inc. P hosphodiesterase 5 (PDE5) is an enzyme that catalyzes the hydrolysis of cyclic guanosine monophosphate, and this activity is essential for smooth muscleecontaining organs, such as the penis, to transit from the relaxed to the contracted state. 1 Inhibi- tion of this activity with pharmacologic agents, known as PDE5 inhibitors (PDE5Is), has a high success rate of treating erectile dysfunction. 2 PDE5 has also been identified in other lower urinary tract organs; thus, considerable interests have developed in the urology field to apply PDE5Is for the treatment of smooth muscleerelated dysfunctions of these organs. 3-5 In 2011, one of such efforts resulted in the US Food and Drug Administration’s approval of tadalafil, a PDE5I, for the treatment of signs and symptoms of benign pros- tate hyperplasia. However, despite this approval, questions have been raised about tadalafil’s mechanism of action because no statistical difference in maximum uri- nary flow rate was observed between tadalafil- and placebo-treated patients. 6,7 Furthermore, published data concerning the level and location of PDE5 expression in the prostate have been highly inconsistent. 5 In regard to PDE5 localization in human prostate, Uckert et al 8 first reported that although a significant amount was detected in the fibromuscular stroma, the majority appeared to be associated with glandular struc- tures. However, in a later study, Zenzmaier et al 9 reported that PDE5 was predominantly expressed in the fibro- muscular stroma, whereas no expression was detectable in the epithelium. In addition, 2 other independent studies by the same research group also failed to detect PDE5 expression in the epithelium. 10,11 But, in this instance, PDE5 expression was determined to be scant in the fibromuscular stroma but predominant in vascular smooth muscle and endothelial cells. However, it should be noted that in these 2 studies the supporting histologic images were acquired respectively at 10 and 4 magnifications, which are too low for discerning the endothelium from the smooth muscle. In regard to PDE5 expression in rat prostate, Morelli et al 11 again reported its presence in vascular endothelial and smooth muscle cells and its absence in the epithe- lium. However, again, the supporting histologic images were acquired at a low magnification of 4, and although Lin Wang and Xiaoyu Zhang contributed equally to the study. Financial Disclosure: Sandhya S. Visweswariah received funding from the Council of Scientific and Industrial Research, Government of India. The other authors declare that they have no relevant financial interests. From the Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San Francisco, CA; the Molecular Biology Laboratory, Andrology Center, Peking University First Hospital, Peking University, Beijing, China; the Department of Urology, Peking University First Hospital and the Institute of Urology, Peking University, Beijing, China; and the Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India Address correspondence to: Ching-Shwun Lin, Ph.D., Department of Urology, University of California, San Francisco, CA 94143-0738. E-mail: clin@urology.ucsf. edu Submitted: September 29, 2014, accepted (with revisions): December 3, 2014 ª 2015 Elsevier Inc. All Rights Reserved http://dx.doi.org/10.1016/j.urology.2014.12.005 0090-4295/15 703.e7