Interaction between testosterone and growth hormone on whole-body protein anabolism occurs in the liver.Birzniece V1, Meinhardt UJ, Umpleby MA, Handelsman DJ, Ho KK.Author informationAbstractCONTEXT: GH
and testosterone both exert protein-anabolic effects and may act
synergistically. Liver and muscle are major sites of protein metabolism.OBJECTIVE: Our
objective was to determine whether the site of GH and testosterone
interaction on protein metabolism is primarily hepatic or extrahepatic.DESIGN: In
this open-label randomized crossover study, the impact on whole-body
protein metabolism of oral (solely hepatic testosterone exposure) and
transdermal (systemic testosterone exposure) testosterone replacement in
the presence or absence of GH was compared.PATIENTS AND INTERVENTION: Eleven
hypopituitary men with GH and testosterone deficiency were randomized
to 2-wk treatments with transdermal testosterone (10 mg) or oral
testosterone (40 mg), with or without GH replacement (0.6 mg/d). The
dose of testosterone administered orally achieves physiological portal
testosterone concentrations without spillover into the systemic
circulation.MAIN OUTCOME MEASURES: 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 estimated at the end of each
treatment.RESULTS: In
the absence of GH, neither transdermal nor oral testosterone affected
LRa or Lox. GH therapy significantly increased LRa, an effect equally
reduced by transdermal and oral testosterone administration. GH
replacement alone did not significantly change Lox, whereas addition of
testosterone treatment reduced Lox, with the effect not significantly
different between transdermal and oral testosterone.CONCLUSIONS: In
the doses used, testosterone stimulates protein anabolism by reducing
protein breakdown and oxidation only in the presence of GH. Because the
net effect on protein metabolism during GH therapy is not different
between systemic and solely hepatic testosterone administration, we
conclude that the liver is the primary site of this hormonal
interaction.