Overexpression of GDNF and FGF-1 in Canine Benign Prostatic Hyperplasia: Evidence for a Pathogenetic Role of Neural Growth Factor.

Abstract

Benign prostatic hyperplasia (BPH) is common in aged dogs, but the pathogenesis has not been clearly elucidated. A total of 33 male Iranian dogs of mixed breed and in three age groups (under 3 years [n&#xa0;=&#xa0;10]; 3-6 years [n&#xa0;=&#xa0;15]; over 6 years [n&#xa0;=&#xa0;8]), were investigated. BPH was confirmed by ultrasonography and histopathology in 13 cases. The highest prevalence of BPH was in the 3-6 years age group (8/15; 53.3%). Examination of sections of prostate that had been stained with Masson's trichrome revealed that the intensity of stromal smooth muscle cell staining (P&#xa0;<0.05) and the number of fibroblasts (P&#xa0;=&#xa0;0.002) were significantly increased in BPH compared with normal prostate glands. Prostate cells from dogs with BPH (n&#xa0;=&#xa0;13) had a significantly higher intensity of cytoplasmic immunolabelling with antibodies against glial cell line-derived neurotrophic factor (GDNF), cytokeratin (CK) AE1/AE3, vimentin, fibroblast growth factor-1 (FGF-1) and prostate-specific antigen (PSA), compared with normal prostate glands (n&#xa0;=&#xa0;20) (P&#xa0;=&#xa0;0.001), except for PSA, which was negative in both normal and BPH affected prostates. The overexpression of GDNF and FGF-1 in stromal and epithelial cells of prostate glands of dogs with BPH suggests that GDNF has a paracrine or autocrine role in stimulating cellular proliferation. GDNF overexpression may also play a pathogenetic role in promoting chronic prostatitis and increasing fibrosis and the smooth muscle component of the prostate gland in BPH.