Upregulation of Phosphodiesterase type 5 in the Hyperplastic Prostate.

Wenhao Zhang,Ning Zang,Xinhua Zhang,Yaoming Jiang,Ping Chen,Xinghuan Wang

doi:10.1038/srep17888

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.

Highlights

Study we used a rat BPH model and human hyperplastic prostate tissue to investigate the expression of genes involved in the major pathways regulating SM tone, with PDE5 emphasized
In parallel with previous observations[11,12], T injection mainly led to a notable involution of acinar epithelium hyperplasia, such as increased acinus amount, papillary fronds protruding into the glandular cavities and thickening of the epithelial layer while the stromal compartment was relatively decreased
Wang et al recently found PDE5 was expressed in both acinar epithelium as well as periacinar SM and lobe-specific PDE5 expression patterns were observed in this study[13]

Summary

Introduction

Bladder weight (mg) study we used a rat BPH model and human hyperplastic prostate tissue to investigate the expression of genes involved in the major pathways regulating SM tone, with PDE5 emphasized. The testosterone (T)-supplementation rat model of BPH was validated through increased weight of the ventral prostate and seminal vesicle (Fig. 1 and Table 1, P < 0 .001) by 1.6-fold and 2-fold, respectively. Differential histopathology was observed between human and rat BPH by H-E and Masson’s trichrome staining.

Results

Conclusion