title: Is transforming growth factor-β signaling activated in human hypertrophied prostate treated by 5-alpha reductase inhibitor?
abstract: OBJECTIVE
  It is well known that androgen deprivation relates to penile fibrosis, so we hypothesize that long-term treatment with 5-alphareductase inhibitors (5ARIs) may increase the risk of fibrosis of prostate.
  
  
  METHODS
  Thirty-two BPH patients who underwent transurethral resection of the prostate were enrolled. The patients were divided into two groups: group one, 16 patients underwent TURP who had been treated with tamsulosin for 2 years; group two, 16 patients underwent TURP who had been treated with combination of tamsulosin and dutasteride for at least 1 year. We evaluated the expressions of nNOS, iNOS, eNOS, TGF-β1, TGF-β2, phosphorylated-Smad2/3 (p-Smad2/3), E-cadherin, N-cadherin, and α-smooth muscle actin in the resected prostate tissues by western blotting, and the TGF-β concentration was determined by ELISA kit.
  
  
  RESULTS
  The expressions of 3 isoforms of NOS were significantly increased in group 2 except of eNOS in lateral prostate, and the expressions of TGF-β1, TGF-β2, and p-Smad2/3 increased about 2-fold compared with group 1. In group 2, the E-cadherin expression decreased while N-cadherin expression increased significantly.
  
  
  CONCLUSIONS
  The overexpression of nNOS may contribute to prostate smooth muscle relaxation; however, long-time treatment with 5 ARI increases the risk of fibrosis of prostate.
authors: Department of Urology of Medical School and Institute for Clinical Medicine, Chonbuk National University and Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University Hospital, Jeonju 561-712, Republic of Korea.
authors: Hye Kyung
authors: HK
authors: Kim
authors: Chen
authors: C
authors: Zhao
authors: Bo Ram
authors: BR
authors: Choi
authors: Han Jung
authors: HJ
authors: Chae
authors: Do Sung
authors: DS
authors: Kim
authors: Jong Kwan
authors: JK
authors: Park
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D003131:Combined Modality Therapy; D006801:Humans; D006984:Hypertrophy / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D000077409:Tamsulosin; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D053781:Transforming Growth Factor beta2 / Q000378:metabolism*; D020728:Transurethral Resection of Prostate
chemical_list: D058891:5-alpha Reductase Inhibitors; D015703:Antigens, CD; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D013449:Sulfonamides; C508960:TGFB1 protein, human; C509041:TGFB2 protein, human; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D019001:Nitric Oxide Synthase; D000077409:Tamsulosin