Is transforming growth factor-β signaling activated in human hypertrophied prostate treated by 5-alpha reductase inhibitor?

Dis Markers. 2013;35(6):679-85. doi: 10.1155/2013/783287. Epub 2013 Nov 6.

Abstract

Background and aim: 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.

Patients and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-alpha Reductase Inhibitors / pharmacology*
  • 5-alpha Reductase Inhibitors / therapeutic use
  • Antigens, CD / metabolism
  • Cadherins / metabolism
  • Combined Modality Therapy
  • Humans
  • Hypertrophy / metabolism
  • Male
  • Nitric Oxide Synthase / metabolism
  • Prostate / drug effects
  • Prostate / metabolism
  • Prostate / pathology
  • Prostate / surgery
  • Prostatic Hyperplasia / drug therapy
  • Prostatic Hyperplasia / metabolism*
  • Prostatic Hyperplasia / surgery
  • Signal Transduction
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Sulfonamides / pharmacology*
  • Sulfonamides / therapeutic use
  • Tamsulosin
  • Transforming Growth Factor beta1 / metabolism*
  • Transforming Growth Factor beta2 / metabolism*
  • Transurethral Resection of Prostate

Substances

  • 5-alpha Reductase Inhibitors
  • Antigens, CD
  • CDH1 protein, human
  • CDH2 protein, human
  • Cadherins
  • SMAD2 protein, human
  • SMAD3 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • Sulfonamides
  • TGFB1 protein, human
  • TGFB2 protein, human
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta2
  • Nitric Oxide Synthase
  • Tamsulosin