title: Low Testosterone Levels Result in Decreased Periurethral Vascularity via an Androgen Receptor-mediated Process: Pilot Study in Urethral Stricture Tissue.
abstract: OBJECTIVE
  To compare expression of androgen receptor (AR) and angiopoietin 1 receptor TIE-2 and vessel density of urethral stricture tissue among eugonadal and hypogonadal men to identify a pathophysiological basis for our observations that low testosterone is associated with urethral atrophy.
  
  
  METHODS
  Among 1200 men having urethroplasty at our institution, we retrospectively identified 11 patients with testosterone levels drawn within 2 years of surgery. Low testosterone was defined as <280 ng/dL and detected in 5 of 11 (45.5%) patients. Urethral tissue samples were analyzed using immunohistochemistry for AR, TIE-2 (a downstream target of activated AR linking it to angiogenesis), and CD31 expression.
  
  
  RESULTS
  Mean testosterone was 179.4 ng/dL for patients classified as having low testosterone and 375.0 ng/dL for controls (P = .003). We found a significant decrease of AR expression (1.11%high power field [HPF] vs 1.62, P = .016), TIE-2 expression (1.84%HPF vs 3.08, P = .006), and vessel counts (44.47 vessels/HPF vs 98.33, P = .004) in men with low testosterone. Expression levels of AR and TIE-2 were directly correlated to testosterone levels (rho: 0.685, P = .029, and rho: 0.773, P = .005, respectively). We did not find a difference in age, radiation, or comorbidities among patients with normal or low testosterone levels, with the exception of higher body mass index in the latter.
  
  
  CONCLUSIONS
  Men with low testosterone levels demonstrate decreased AR and TIE-2 expression and lower vessel counts in periurethral tissue samples of urethral strictures. Our results provide a rationale for a mechanistic relationship between low testosterone levels and decreased periurethral vascularity that may contribute to urethral atrophy in patients with urethral strictures.
authors.affiliation: Department of Urology, UT Southwestern, Dallas, TX.
authors.forename: Matthias D
authors.initials: MD
authors.lastname: Hofer
authors.affiliation: Department of Pathology, UT Southwestern, Dallas, TX.
authors.forename: Payal
authors.initials: P
authors.lastname: Kapur
authors.affiliation: Department of Urology, UT Southwestern, Dallas, TX.
authors.forename: Billy H
authors.initials: BH
authors.lastname: Cordon
authors.affiliation: Department of Pathology, UT Southwestern, Dallas, TX.
authors.forename: Farrah
authors.initials: F
authors.lastname: Hamoun
authors.affiliation: Department of Molecular Genetics, UT Southwestern, Dallas, TX.
authors.forename: David
authors.initials: D
authors.lastname: Russell
authors.affiliation: Department of Urology, UT Southwestern, Dallas, TX.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Scott
authors.affiliation: Department of Urology, UT Southwestern, Dallas, TX.
authors.forename: Claus G
authors.initials: CG
authors.lastname: Roehrborn
authors.affiliation: Department of Urology, UT Southwestern, Dallas, TX. Electronic address: allen.morey@utsouthwestern.edu.
authors.forename: Allen F
authors.initials: AF
authors.lastname: Morey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D007006:Hypogonadism / Q000150:complications / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D012189:Retrospective Studies; D013739:Testosterone / Q000097:blood*; D014521:Urethra / Q000098:blood supply*; D014525:Urethral Stricture / Q000209:etiology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011944:Receptors, Androgen; D013739:Testosterone; D042787:Receptor, TIE-2