Growth hormone decreases muscle glutamine production and stimulates protein synthesis in hypercatabolic patients.
We determined the effects of 24-h recombinant human growth hormone (rhGH) infusion into a femoral artery on leg muscle protein kinetics, amino acid transport, and glutamine metabolism in eight adult hypercatabolic trauma patients. Metabolic pathways were assessed by leg arteriovenous catheterization and muscle biopsies with the use of stable amino acid isotopes. Muscle mRNA levels of selected enzymes were determined by competitive PCR. rhGH infusion significantly accelerated the inward transport rates of phenylalanine and leucine and protein synthesis, whereas the muscle protein degradation rate and cathepsin B and UbB polyubiquitin mRNA levels were not significantly modified by rhGH. rhGH infusion decreased the rate of glutamine de novo synthesis and glutamine precursor availability, total branched-chain amino acid catabolism, and nonprotein glutamate utilization. Thus net glutamine release from muscle into circulation significantly decreased after rhGH administration ( approximately 50%), whereas glutamine synthetase mRNA levels increased after rhGH infusion, possibly to compensate for reduced glutamine precursor availability. We conclude that, after trauma, the anticatabolic action of rhGH is associated with a potentially harmful decrease in muscle glutamine production.
Biolo
G
G
Istituto di Clinica Medica, Trieste 34149, Italy. gianni.biolo@clmed.univ.trieste.it
Iscra
F
F
Bosutti
A
A
Toigo
G
G
Ciocchi
B
B
Geatti
O
O
Gullo
A
A
Guarnieri
G
G
D000328:Adult; D000596:Amino Acids / Q000097:blood; D001704:Biopolymers / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D002401:Cathepsin B / Q000235:genetics / Q000378:metabolism; D004750:Enteral Nutrition; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000097:blood*; D006801:Humans; D007261:Infusions, Intra-Arterial; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007866:Leg / Q000098:blood supply / Q000502:physiology; D008297:Male; D009104:Multiple Trauma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010288:Parenteral Nutrition; D025821:Polyubiquitin; D014176:Protein Biosynthesis; D012313:RNA / Q000378:metabolism; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects / Q000502:physiology*
D000596:Amino Acids; D001704:Biopolymers; D007328:Insulin; D014452:Ubiquitins; D005973:Glutamine; D025821:Polyubiquitin; D019382:Human Growth Hormone; D012313:RNA; D007334:Insulin-Like Growth Factor I; D002401:Cathepsin B; D005974:Glutamate-Ammonia Ligase