title: Testosterone prevents protein loss via the hepatic urea cycle in human.
abstract: BACKGROUND
  The urea cycle is a rate-limiting step for amino acid nitrogen elimination. The rate of urea synthesis is a true indicator of whole-body protein catabolism. Testosterone reduces protein and nitrogen loss. The effect of testosterone on hepatic urea synthesis in humans has not been studied.
  
  
  OBJECTIVE
  To determine whether testosterone reduces hepatic urea production.
  
  
  METHODS
  An open-label study.
  
  
  METHODS
  Eight hypogonadal men were studied at baseline, and after two weeks of transdermal testosterone replacement (Testogel, 100 mg/day).
  
  
  METHODS
  The rate of hepatic urea synthesis was measured by the urea turnover technique using stable isotope methodology, with15N2-urea as tracer. Whole-body leucine turnover was measured, from which leucine rate of appearance (LRa), an index of protein breakdown and leucine oxidation (Lox), a measure of irreversible protein loss, were calculated.
  
  
  RESULTS
  Testosterone administration significantly reduced the rate of hepatic urea production (from 544.4 ± 71.8 to 431.7 ± 68.3 µmol/min;P< 0.01), which was paralleled by a significant reduction in serum urea concentration. Testosterone treatment significantly reduced net protein loss, as measured by percent Lox/LRa, by 19.3 ± 5.8% (P< 0.05). There was a positive association between Lox and hepatic urea production at baseline (r2= 0.60,P< 0.05) and after testosterone administration (r2= 0.59,P< 0.05).
  
  
  CONCLUSIONS
  Testosterone replacement reduces protein loss and hepatic urea synthesis. We conclude that testosterone regulates whole-body protein metabolism by suppressing the urea cycle.
authors.affiliation: School of MedicineWestern Sydney University, Penrith, New South Wales, Australia.|Department of Diabetes and EndocrinologyBlacktown Hospital, Blacktown, New South Wales, Australia.
authors.forename: Teresa
authors.initials: T
authors.lastname: Lam
authors.affiliation: Bioanalytical Mass Spectrometry Facility and School of Medical SciencesUniversity of New South Wales, New South Wales, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Poljak
authors.affiliation: School of MedicineWestern Sydney University, Penrith, New South Wales, Australia.|Department of Diabetes and EndocrinologyBlacktown Hospital, Blacktown, New South Wales, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: McLean
authors.affiliation: School of MedicineWestern Sydney University, Penrith, New South Wales, Australia.|Garvan Institute of Medical ResearchSydney, New South Wales, Australia.
authors.forename: Neha
authors.initials: N
authors.lastname: Bahl
authors.affiliation: Garvan Institute of Medical ResearchSydney, New South Wales, Australia.|Centres of Health ResearchPrincess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: Ken K Y
authors.initials: KKY
authors.lastname: Ho
authors.affiliation: School of MedicineWestern Sydney University, Penrith, New South Wales, Australia.|Department of Diabetes and EndocrinologyBlacktown Hospital, Blacktown, New South Wales, Australia.|Garvan Institute of Medical ResearchSydney, New South Wales, Australia.|School of MedicineUniversity of New South Wales, New South Wales, Australia.
authors.forename: Vita
authors.initials: V
authors.lastname: Birzniece
mesh_terms: D000328:Adult; D001823:Body Composition / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013739:Testosterone / Q000494:pharmacology* / Q000627:therapeutic use; D014508:Urea / Q000378:metabolism*
chemical_list: D013739:Testosterone; D014508:Urea