Finasteride accelerates prostate wound healing after thulium laser resection through DHT and AR signalling

Cell Prolif. 2018 Jun;51(3):e12415. doi: 10.1111/cpr.12415. Epub 2017 Nov 30.

Abstract

Objectives: Urinary tract infection, urinary frequency, urgency, urodynia and haemorrhage are common post-operative complications of thulium laser resection of the prostate (TmLRP). Our study mainly focuses on the role of finasteride in prostate wound healing through AR signalling.

Materials and methods: TmLRP beagles were randomly distributed into different treatment groups. Serum and intra-prostatic testosterone and DHT level were determined. Histological analysis was conducted to study the re-epithelialization and inflammatory response of the prostatic urethra in each group. We investigated the role of androgen in proliferation and inflammatory response in prostate. In addition, the effects of TNF-α on prostate epithelium and stromal cells were also investigated.

Results: Testosterone and DHT level increased in testosterone group and DHT decreased in finasteride group. Accelerated wound healing of prostatic urethra was observed in the finasteride group. DHT suppressed proliferation of prostate epithelium and enhanced inflammatory response in prostate. We confirmed that DHT enhanced macrophages TNF-α secretion through AR signalling. TNF-α suppressed proliferation of prostate epithelial cells and retarded cell migration. TNF-α also played a pivotal role in suppressing fibroblasts activation and contraction.

Conclusion: Testosterone treatment repressed re-epithelialization and wound healing of prostatic urethra. Finasteride treatment may be an effective way to promote prostate re-epithelialization.

Keywords: DHT; TNF-α; TmLRP; finasteride; wound healing.

MeSH terms

  • Animals
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Dihydrotestosterone / metabolism
  • Dogs
  • Down-Regulation
  • Drug Evaluation, Preclinical
  • Epithelium / physiopathology
  • Finasteride / pharmacology
  • Finasteride / therapeutic use*
  • Humans
  • Laser Therapy
  • Male
  • Prostate / physiopathology*
  • Prostate / surgery
  • Prostatic Hyperplasia / surgery
  • Proto-Oncogene Proteins c-myc / metabolism
  • Receptors, Androgen / metabolism
  • Receptors, Tumor Necrosis Factor, Type I / metabolism
  • Signal Transduction*
  • Testosterone / physiology
  • Tumor Necrosis Factor-alpha / metabolism
  • Wound Healing / drug effects

Substances

  • Proto-Oncogene Proteins c-myc
  • Receptors, Androgen
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha
  • Dihydrotestosterone
  • Testosterone
  • Finasteride