AB51. PDE5 expression in the prostate: where is it really?

Abstract

PDE5 inhibitor Tadalafil has been approved for the treatment of BPH symptoms, but where PDE5 is expressed in the prostate remains a mystery. In the literature five studies have reported immunolocalization of PDE5 in the prostate. Uckert et al. concluded that PDE5 is mainly expressed in the glandular structure, but Zenzmaier et al., Fibbi et al., Morelli et al., and Zhang et al. all said that PDE5 is undetectable in the epithelium. Still, while Zenzmaier et al. and Zhang et al. found that PDE5 is mainly expressed in the fibromuscular stroma, Fibbi et al. and Morelli et al. said that PDE5 is undetectable in the fibromuscular stroma and is mainly expressed in the vascular endothelium and smooth muscle. However, it should be noted that the histological images in the latter studies were acquired at 4× or 10× magnifications, which are too low for discerning such structures.In each of these five studies PDE5 expression was investigated only as a companion or side issue. In fact, regardless of the findings, the location of PDE5 expression has little or no relevance to these studies’ main outcomes. However, when put together for reference or review, these studies cause considerable confusions. As such, we recently conducted a dedicated investigation on PDE5 expression in rat prostate. By using Western blot analysis we found that PDE5 was expressed at a significantly lower level in dorsal lobe (DL) than in ventral lobe (VL) or lateral lobe (LL). By using immunohistochemistry and immunofluorescence we found that PDE5 was expressed in both acinar epithelium and periacinar smooth muscle. However, while similar levels of smooth muscle PDE5 expression were observed in all three prostatic lobes, significantly lower level of epithelial PDE5 expression was found in DL compared to VL or LL. In prostatic blood vessels PDE5 expression was clearly visible in the endothelium but not as easily detectable in the smooth muscle. Regardless, the acinar wall, not the blood vessel wall, is the predominant PDE5 expression site in rat prostate.