title: Testosterone effect on the expression of genes that mediate testosterone metabolism and genes that mediate the effect of those metabolites on the prostate.
abstract: OBJECTIVE
  The aim of this study was to investigate the effect of testosterone treatment on the proliferation index and the mRNA expression levels of 5α-reductase, CYP7B1, androgen receptor (AR), and estrogen receptor β (ΕRβ) in the canine prostate.
  
  
  METHODS
  Immature dogs were treated with testosterone for one month, after which prostate gland growth was assessed by comparing the proliferation index in prostates from testosterone-treated dogs with that of untreated control dogs. The relative mRNA expression levels of the aforementioned genes in the prostate glands of testosterone-treated and untreated dogs were determined by real time PCR.
  
  
  RESULTS
  Testosterone treatment induced a highly significant reduction in proliferation index in prostate gland. This inhibition of prostate gland growth was associated with differential mRNA expression of 5α-reductase, CYP7B1, AR, and ΕRβ by the prostate gland of testosterone-treated dogs, as compared to that of untreated dogs. While the expression levels of 5α-reductase and CYP7B1 mRNA were significantly down-regulated by testosterone treatment, the expression level of ER-β mRNA was highly up-regulated. In contrast, AR mRNA expression was not significantly altered.
  
  
  CONCLUSIONS
  Prostate gland proliferation appeared to be associated with the expression levels of genes that encode proteins that control intra-prostatic levels of testosterone metabolites and their respective receptors. Testosterone treatment may regulate gene expression in the prostate to generate a phenotype that suppresses growth-promoting signaling through AR and enhances anti-proliferative signaling through ERβ. Therefore, targeting disturbances of this genetic machinery in benign prostate hyperplasia and prostate cancer is of a therapeutic potential.
authors: Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA. falah@just.edu.jo
authors: Falah
authors: F
authors: Shidaifat
authors: Young C
authors: YC
authors: Lin
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D000728:Androgens / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004285:Dogs; D015536:Down-Regulation / Q000187:drug effects*; D047629:Estrogen Receptor beta / Q000235:genetics; D008297:Male; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013250:Steroid Hydroxylases / Q000235:genetics; D013739:Testosterone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000728:Androgens; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013739:Testosterone; C004648:testosterone enanthate; D013250:Steroid Hydroxylases; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase