Gene Expression Profiling of Androgen Deficiency Predicts a Pathway of Prostate Apoptosis That Involves Genes Related to Oxidative Stress

Endocrinology. 2002 Dec;143(12):4897-906. doi: 10.1210/en.2002-220327.

Abstract

Androgens are critical for prostate development, growth, and functions. In general, they support proliferation and prevent cell death of prostatic epithelial cells. Here, we studied changes of gene expression after castration and testosterone replacement therapy in the rat ventral prostate using cDNA microarrays analysis. We could identify 230 genes that were regulated in either experimental condition. Using hierarchical clustering analysis, different groups of genes could be detected according to their expression pattern. This enabled us to distinguish the putative androgen-responsive genes from the secondary-responsive ones. Among genes that altered during castration and testosterone replacement, a set of oxidative stress-related genes, including thioredoxin, peroxiredoxin 5, superoxide dismutase 2, glutathione peroxidase 1, selenoprotein 15 kDa, microsomal glutathione-S-transferase, glutathione reductase, and epoxide hydrolase, were changed by castration. We hypothesize that modulation of redox status can be a factor of relevance in androgen withdrawal-induced prostate apoptosis. In selective cases, quantitative RT-PCR was used to confirm changes in gene expression. Immunohistochemistry was performed to detect thioredoxin and ezrin. Both of these were detected in the prostate and seem to be regulated in a similar manner as shown by gene expression analysis. In conclusion, gene expression profiling provides a unique opportunity for understanding the molecular mechanisms of androgen actions in prostate gland.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / deficiency*
  • Animals
  • Apoptosis*
  • Cytoskeletal Proteins
  • Epoxide Hydrolases / genetics
  • Gene Expression Profiling*
  • Glutathione Peroxidase / genetics
  • Glutathione Reductase / genetics
  • Glutathione Transferase / genetics
  • Hormone Replacement Therapy
  • Immunohistochemistry
  • Male
  • Orchiectomy
  • Oxidation-Reduction
  • Oxidative Stress / genetics*
  • Peroxidases / genetics
  • Peroxiredoxins
  • Phosphoproteins / analysis
  • Prostate / cytology*
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Superoxide Dismutase / genetics
  • Testosterone / administration & dosage
  • Thioredoxins / analysis
  • Thioredoxins / genetics

Substances

  • Androgens
  • Cytoskeletal Proteins
  • Phosphoproteins
  • ezrin
  • Testosterone
  • Thioredoxins
  • Peroxidases
  • Peroxiredoxins
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • superoxide dismutase 2
  • Glutathione Reductase
  • Glutathione Transferase
  • Epoxide Hydrolases