Expression of cavernous transforming growth factor-beta1 and its type II receptor in patients with erectile dysfunction.

It has been hypothesized that transforming growth factor-beta1 (TGF-beta1) signalling is involved in erectile dysfunction (ED). This study was undertaken to elucidate in detail whether expression of TGF-beta1 and its type II receptor is clinically related to various causes of ED. Fifty-four patients with ED and 24 potent men were the subjects of this study. After multidisciplinary work-up, the ED was classified as psychogenic (n = 6), neurogenic (n = 15), or vasculogenic (n = 33). In every subject, percutaneous cavernous biopsy was performed using a Biopty gun. Masson's trichrome staining was used to quantitate collagen fibres and immunohistochemical staining to evaluate both TGF-beta1 and its type II receptor by scoring the intensity of immunoreactivity (score 0-6). Collagen fibres were significantly more abundant in men with vasculogenic ED (72.7 +/- 17.7%) than in control subjects (43.3 +/- 11.2%) or those with psychogenic (45.0 +/- 12.2%) or neurogenic (51.3 +/- 20.3%) ED (p < 0.01). Expression of TGF-beta1 was significantly greater in vasculogenic ED (4.3 +/- 1.3) than in the control subjects (2.4 +/- 0.9) or psychogenic ED (2.0 +/- 0.6) groups (p < 0.01). Type II receptor expression was also significantly increased in vasculogenic ED (3.9 +/- 1.3) compared with control (2.2 +/- 0.7) and psychogenic (2.2 +/- 0.8) or neurogenic (2.6 +/- 1.3) ED (p < 0.01). Of the ED groups, both the hyperlipidaemia and the atherosclerosis patients showed significantly more fibrosis than those without the condition (p < 0.05). The abundance of collagen fibres correlated well with both TGF-beta1 expression (gamma = 0.81; p < 0.001) and receptor II expression (gamma = 0.83; p < 0.001). These results suggest that TGF-beta1 and its receptor II pathway are involved in cavernous fibrosis and ED in man. Patients with vascular risk factors such as hyperlipidaemia and atherosclerosis are liable to ED by activation of this pathway.