| Objectives:Phosphodiesterase type 5 inhibitors (PDE5i) which are the first-line therapy for erectile dysfunction, have been found effective in treatment of BPH and LUTS in clinical trials. This study is to investigate the effect of testosterone on PDE5 expression in the rat prostate.Materials and Methods:Thirty male adult Sprague-Dawley rats (Weighing 215-275g) were used. Rats were randomly divided into 3 groups:Sham-operated (control) group (n=10), surgical castrated group (n=10) and testosterone (T) supplemented group (n=10). After surgery, all rats were kept 2 weeks, the prostate and seminal vesicle were removed and weighted when the animals were killed. The PDE5 expression was quantified by both real-time RT-PCR and Western blot analysis and localized by immunohistochemistry in the prostate tissue.Results:The prostate and seminal vesicle atrophy were observed in surgical castrated rats which can be prevented by T supplementation. The prostate weight were 744.74±15.87mg,155.53±8.55mg,861.90±10.66mg for control, surgical castrated group and T supplemented group, respectively (P<0.01 vs control). The seminal vesicle weight were 1539.27±81.93mg (control),257.01±10.88mg (castration), and 2647.10±148.66mg (T replacement), respectively (P<0.01 vs control).Compared with Control group, real time RT-PCR showed surgical castration induced a significant reduction of PDE5 gene expression (P<0.01), while T supplemented could restore PDE5 gene expression, there was no statistically significances between the T supplementation and Control group (P>0.05). Western blot analysis simlilarly found castration induced a significant reduction of PDE5 protein expression(9.20±2.16) (P<0.01), T supplemented also could restore PDE5 proterin expression, there was no statistically significances between the T supplementation 15.07±3.76) and Control group(13.48±1.92)(P>0.05). The PDE5 was immunolocalized in endothelial and smooth muscle cells. Surgical castrated also induced a significant reduction of PDE5 stain (P<0.01). There was no statistically significances between the T supplementated and Controled group (P>0.05).Conclusions:For the first time, we found that testosterone positively regulates PDE5 gene and protein expression in the rat prostate. Our novel findings suggest that inhibition of PDE5 signaling pathway maybe a new mechanism for the anti-androgen treatment for BPH. |
