O.53 Growth hormone decreases glutamine production while stimulating muscle protein synthesis in severely traumatized patients

The short-term effects of growth hormone (GH) on skeletal muscle protein synthesis and degradation in normal humans are unknown. We studied seven postabsorptive healthy men (age 18-23 yr) who received GH (0.014 micrograms.kg-1.min-1) via intrabrachial artery infusion for 6 h. The effects of GH on forearm amino acid and glucose balances and on forearm amino acid kinetics [( 3H]Phe and [14C]Leu) were determined after 3 and 6 h of the GH infusion. Forearm deep vein GH rose to 35 +/- 6 ng/ml in response to GH, whereas systemic levels of GH, insulin, and insulin-like growth factor I (IGF-I) were unchanged. Forearm glucose uptake did not change during the study. After 6 h, GH suppressed forearm net release (3 vs. 6 h) of Phe (P less than 0.05), Leu (P less than 0.01), total branched-chain amino acids (P less than 0.025), and essential neutral amino acids (0.05 less than P less than 0.1). The effect on the net balance of Phe and Leu was due to an increase in the tissue uptake for Phe (71%, P less than 0.05) and Leu (37%, P less than 0.005) in the absence of any significant change in release of Phe or Leu from tissue. In the absence of any change in systemic GH, IGF-I, or insulin, these findings suggest that locally infused GH stimulates skeletal muscle protein synthesis. These findings have important physiological implications for both the role of daily GH pulses and the mechanisms through which GH can promote protein anabolism.

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Growth hormone decreases muscle glutamine production and stimulates protein synthesis in hypercatabolic patients

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2000.279.2.e323 ◽

2000 ◽

Vol 279 (2) ◽

pp. E323-E332 ◽

Cited By ~ 34

Author(s):

Gianni Biolo ◽

Fulvio Iscra ◽

Alessandra Bosutti ◽

Gabriele Toigo ◽

Beniamino Ciocchi ◽

...

Keyword(s):

Growth Hormone ◽

Protein Synthesis ◽

Amino Acid ◽

De Novo ◽

Muscle Protein ◽

Recombinant Human Growth Hormone ◽

Glutamine Metabolism ◽

Trauma Patients ◽

Mrna Levels ◽

Glutamine Production

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 (∼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.

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Effects of Growth Hormone on Leptin Metabolism and Energy Expenditure in Hemodialysis Patients with Protein-Calorie Malnutrition

Journal of the American Society of Nephrology ◽

10.1681/asn.v11112106 ◽

2000 ◽

Vol 11 (11) ◽

pp. 2106-2113

Author(s):

GIACOMO GARIBOTTO ◽

ANTONINA BARRECA ◽

ANTONELLA SOFIA ◽

RODOLFO RUSSO ◽

FULVIO FIORINI ◽

...

Keyword(s):

Growth Hormone ◽

Protein Synthesis ◽

Energy Expenditure ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Resting Energy Expenditure ◽

Hemodialysis Patients ◽

Gh Treatment ◽

Peripheral Tissues

Abstract. The relationships among growth hormone (GH), leptin, and resting energy expenditure (REE) are not understood. It has been reported that in malnourished hemodialysis patients, GH increases muscle protein synthesis, a process that requires energy. The present study evaluated the arterial levels and the forearm exchange of leptin, as well as the REE of the same patients during their participation in the same study, in four sequential 6-wk periods: I, baseline; II, GH treatment; III, washout; and IV, GH + intradialytic parenteral nutrition. During periods II and IV, patients received GH (5 mg three times per week). REE rose by 5% in period II, declined during period III, and rose by 7% during period IV. Basal leptin levels were low (2.0 ± 0.19 ng/L). Insulin and leptin levels, as well as leptin release from the forearm, were unchanged during periods I through III but rose (+ 36%; P < 0.05) during period IV. Changes in arterial leptin were directly related to changes in forearm leptin release (P < 0.002), indicating a role of leptin production by peripheral tissues on leptinemia. Changes in leptin release were directly related to insulin (P < 0.001) and, less consistently, to insulin-like growth factor-binding protein-1 levels (P < 0.02). Similarly, variations in leptin levels were directly related to insulin (P < 0.01). Variations in REE were not related to variations in leptin or insulin levels but to changes in muscle protein synthesis (P < 0.025). The data show that in malnourished hemodialysis patients, treatment with GH is not invariably associated with an increase in leptin production. An increase in leptin release by peripheral tissues and leptin levels occurs only in the setting of hyperinsulinemia. The increase in REE that is induced by treatment with GH is not dependent on changes in leptin but is largely accounted for by the energy cost of the stimulation of muscle protein synthesis.

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Effects of growth hormone and an antiserum to rat growth hormone on serum IGF-I and muscle protein synthesis and accretion in the rat

Journal of Endocrinology ◽

10.1677/joe.0.1390395 ◽

1993 ◽

Vol 139 (3) ◽

pp. 395-401 ◽

Cited By ~ 4

Author(s):

R. M. Palmer ◽

D. J. Flint ◽

J. C. MacRae ◽

F. E. Fairhurst ◽

L. A. Bruce ◽

...

Keyword(s):

Growth Hormone ◽

Protein Synthesis ◽

Protein Content ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Polyclonal Antiserum ◽

Whole Body ◽

Total Protein Content ◽

Plantaris Muscle ◽

Igf I

ABSTRACT Rats were injected twice daily for up to 10 days with GH or with a polyclonal antiserum to rat GH, commencing at 21–22 days of age. Administration of bovine or human GH (1 mg/day) improved whole body growth rates by 22% and 29% respectively. Plantaris muscle mass was also increased, by 7 and 14% respectively. Anti-GH injected twice daily resulted in a 7% decrease in body weight at 4 days and a 10% reduction by 10 days. Similar decreases were observed in the total protein content of plantaris and soleus muscles. The decrease in the fractional rate of protein synthesis was proportionately greater than the decline in protein content in plantaris muscle whereas in the soleus no change in the rate of protein synthesis was observed, suggesting that the effect on this muscle was due to an increase in the rate of protein degradation. Serum total IGF-I was unchanged by treatment with either GH or anti-GH while the amount of hepatic IGF-I mRNA was also unaffected by anti-GH injection. These data are consistent with a direct effect of GH or an effect mediated by an autocrine/paracrine mechanism of action on muscle but do not support a role for serum total IGF-I as an endocrine mediator of GH action. Journal of Endocrinology (1993) 139, 395–401

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