title: Upregulation of Phosphodiesterase type 5 in the Hyperplastic Prostate.
abstract: Both erectile dysfunction (ED) and lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) are common in the aging male. Numerous clinical trials have demonstrated the efficacy and safety of phosphodiesterase type 5 inhibitors (PDE5-Is) for treating LUTS/BPH with/without ED. However, the influence of BPH on prostatic PDE5 expression has never been studied. A testosterone-induced rat model of BPH was developed and human hyperplastic prostate specimens were harvested during cystoprostatectomy. PDE5, nNOS, eNOS and α1-adrenoreceptor subtypes (α1aARs, α1bARs and α1dARs) were determined with real-time RT-PCR for rat tissues whilst PDE5 and α1-adrenoreceptor subtypes were determined in human samples. PDE5 was further analyzed with Western-blot and histological examination. Serum testosterone was measured with ELISA. The rat BPH model was validated as having a significantly enlarged prostate. PDE5 localized mainly in fibromuscular stroma in prostate. Our data showed a significant and previously undocumented upregulation of PDE5 in both rat and human BPH, along with increased expression of nNOS and α1dARs for rat tissues and α1aARs for human BPH. The upregulation of PDE5 in the hyperplastic prostate could explain the mechanism and contribute to the high effectiveness of PDE5-Is for treating LUTS/BPH. Fibromuscular stroma could be the main target for PDE5-Is within prostate.
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R.China.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Medical Scientific Research Center of Guangxi Medical University, Nanning 530021, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zang
authors.affiliation: Department of Urology, the First People's Hospital of Xiaochang, Hubei 432900, P.R.China.
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R.China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R.China.
authors.forename: Xinghuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, P.R.China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D011467:Prostate / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013739:Testosterone / Q000097:blood / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D013739:Testosterone; D052248:Nitric Oxide Synthase Type I; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5