Possible autocrine loop of the epidermal growth factor system in patients with benign prostatic hyperplasia treated with finasteride: a placebo-controlled randomized study

BJU Int. 2002 Apr;89(6):583-90. doi: 10.1046/j.1464-410x.2002.02665.x.

Abstract

Objective: To analyse the expression of the epidermal growth factor (EGF) system in prostate tissue and secretions obtained from patients with benign prostatic hyperplasia (BPH) treated with or without finasteride (which primarily targets the androgen-sensitive secretory epithelial cells in the prostate, with little effect on basal epithelial and stromal cells).

Patients and methods: The expression of the EGF system was evaluated by enzyme-linked immunosorbent assay and immunohistochemistry in samples of prostate tissue and secretions from patients with BPH randomized for treatment with finasteride or placebo for 3 months before surgery.

Results: Prostate tissue expressed the EGF receptor (HER1) and HER2, and the ligands EGF, transforming growth factor alpha (TGFalpha), heparin-binding (HB) EGF, betacellulin and amphiregulin. Treatment with finasteride produced greater concentrations of amphiregulin (P < 0.05) than did placebo, did not change the level of TGFalpha, HER1 and HER2, and tended to decrease the concentration of EGF, betacellulin and HB-EGF in prostate tissue. Using immunohistochemistry, HER1 and TGFalpha were both localized to the basal epithelial cells, and there was a strong positive correlation among the tissue concentrations of HER1, HER2 and TGFalpha. Amphiregulin localized to the luminal secretory epithelium. Prostate secretions contained only EGF, which was at levels approximately 150 times higher than in prostate tissue; treatment with finasteride did not affect the concentration of EGF in prostate secretion.

Conclusions: There were only minor changes in the expression of TGFalpha, HER1 and HER2 after finasteride treatment. This may represent an important system for the continuous growth and homeostasis of the androgen-independent basal epithelial cells in the prostate.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphiregulin
  • Betacellulin
  • EGF Family of Proteins
  • Epidermal Growth Factor / metabolism*
  • ErbB Receptors / metabolism
  • Finasteride / therapeutic use*
  • Glycoproteins / metabolism
  • Growth Substances / metabolism
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins*
  • Male
  • Prospective Studies
  • Prostatic Hyperplasia / drug therapy*
  • Prostatic Hyperplasia / metabolism
  • Receptor, ErbB-2 / metabolism
  • Transforming Growth Factor alpha / metabolism

Substances

  • AREG protein, human
  • Amphiregulin
  • BTC protein, human
  • Betacellulin
  • EGF Family of Proteins
  • Glycoproteins
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Transforming Growth Factor alpha
  • Finasteride
  • Epidermal Growth Factor
  • ErbB Receptors
  • Receptor, ErbB-2