Oral Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Testosterone prevents protein loss via the hepatic urea cycle (#112)

Teresa Lam 1 2 , Mark McLean 3 , Neha Bahl 2 4 , Anne Poljak 5 , Ken K.Y. Ho 4 6 , Vita Birzniece 1 2 4 7
  1. Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW, Australia
  2. School of Medicine, Western Sydney University, Penrith, NSW, Australia
  3. Department of Diabetes and Endocrinology, Blacktown Hospital, Blacktown, NSW, Australia
  4. Garvan Institute of Medical Research, Sydney, NSW, Australia
  5. Bioanalytical Mass Spectometry Facility and School of Medical Sciences, University of New South Wales, Randwick, NSW, Australia
  6. Centres of Health Research, Princess Alexandra Hospital, Brisbane, Queensland, Australia
  7. School of Medicine, University of New South Wales, Randwick, NSW, Australia

Context: Testosterone is a major anabolic hormone that reduces protein and nitrogen loss. As the hepatic 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. The effect of testosterone on hepatic urea cycle in humans has not been studied. We hypothesize that testosterone down-regulates the hepatic urea cycle, thereby preventing systemic protein loss.

Objective: To investigate the effect of testosterone on hepatic urea production.

Design: In this open label study, testosterone replacement was initiated in hypogonadal men, and its effects on hepatic urea production and whole-body protein metabolism were studied.  

Patients and Intervention: Eight hypogonadal men were studied at baseline, and after two weeks of testosterone replacement (Testogel, 100 mg/day).

Main Outcomes Measures: The rate of hepatic urea synthesis was measured by a recently developed urea turnover technique using stable isotope methodology, with 15N2-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: At baseline, there was a significant association between Lox and the rate of urea synthesis. 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 Lox by 18.1 ± 6.9% (p < 0.05). Net protein loss, as measured by percent Lox/LRa, was reduced by 19.3 ± 5.8 % (p < 0.05).

Conclusion: Testosterone replacement reduces protein loss and hepatic urea synthesis. We conclude that testosterone may regulate protein metabolism and muscle mass via suppressing the urea cycle.