Interaction between testosterone and growth hormone on whole-body protein anabolism occurs in the liver.
BACKGROUND
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.


METHODS
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.


METHODS
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.


METHODS
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.
Garvan Institute of Medical Research and Department of Endocrinology, St Vincent’s Hospital, Sydney, New South Wales 2010, Australia.
Vita
V
Birzniece
Udo J
UJ
Meinhardt
Margot A
MA
Umpleby
David J
DJ
Handelsman
Ken K Y
KK
Ho
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D004338:Drug Combinations; D004347:Drug Interactions; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000172:deficiency / Q000494:pharmacology*; D006801:Humans; D007018:Hypopituitarism / Q000188:drug therapy* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008660:Metabolism / Q000187:drug effects; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism*; D013739:Testosterone / Q000008:administration & dosage / Q000172:deficiency / Q000494:pharmacology*; D055815:Young Adult
D004338:Drug Combinations; D011506:Proteins; D019382:Human Growth Hormone; D013739:Testosterone