Growth hormone acutely stimulates skeletal muscle but not whole-body protein synthesis in humans

doi:10.1016/0026-0495(93)90285-V

Metabolism

Volume 42, Issue 9, September 1993, Pages 1223-1227

https://doi.org/10.1016/0026-0495(93)90285-V Get rights and content

Abstract

In a previous study, a 6-hour local infusion of growth hormone (GH) into the brachial artery of normal subjects stimulated net muscle protein anabolism by augmenting skeletal muscle protein synthesis. In the present study, we examined whether systemically infused GH affects forearm and whole-body protein metabolism. Normal volunteers aged 18 to 24 years (n = 8) were given an 8-hour systemic infusion of ³H-phenylalanine and ¹⁴C-leucine. Between 90 and 120 minutes of tracer infusion, basal samples for determination of forearm and whole-body amino acid kinetics were taken. GH was then infused at 0.06 μg/kg/min, increasing GH concentration from 2.4 ± 0.3 to 32 ± 3 ng/mL. Systemic insulin-like growth factor 1 (IGF-1) level increased from 224 ± 20 to 262 ± 21 ng/mL (basal v 6-hour, P < .01). By 6 hours, GH suppressed forearm phenylalanine and leucine net release (each P < .05) by increasing ³H-phenylalanine (66%, P < .05) and ¹⁴C-leucine (13%, P < .05) extraction or disposal (R_d). Whole-body leucine rate of appearance ([R_a] an index of whole-body proteolysis) and nonoxidative leucine R_d (whole-body protein synthesis) did not change over the course of the GH infusion, whereas oxidative leucine R_d decreased (20%, P < .03). Acute stimulation of muscle but not whole-body protein synthesis by systemically infused GH suggests that muscle protein is acutely and specifically regulated by GH.

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With regard to protein catabolism, administration of GH alone had no obvious effect on catabolism of proteins, but it suppressed the enhanced effect of glucocorticoid on protein catabolism [21]. Other studies reported that short-term GH administration had no effect on protein catabolism in healthy volunteers [22–24]. Considered together, these studies suggest that GH seems to increase protein synthesis and inhibit protein catabolism under critical condition although further studies are needed to determine the net effect of short-term administration of GH on albumin synthesis.
Glycated albumin (GA) does not reflect glycemic control in patients with disorders of albumin metabolism. In the present study, we examined GA concentrations in acromegalic patients with growth hormone (GH) excess.
We studied the hormonal status of 29 acromegalic patients (10 patients had diabetes mellitus and the remaining 19 patients were non-diabetic), 20 patients with type 2 diabetes mellitus and 38 non-diabetic subjects matched for age, sex and body mass index.
Serum GA concentrations, but not those of fasting plasma glucose, 2-h post-load plasma glucose and HbA1c, were significantly higher in non-diabetic acromegalic patients compared with non-diabetic control subjects. Serum GA concentrations, but not those of fasting plasma glucose and HbA1c, were significantly higher in diabetic acromegalic patients compared with patients with type 2 diabetes mellitus.
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Citation Excerpt :
In addition it has been reported that 6 weeks of high dose GH treatment to malnourished hemodialysis patients stimulated muscle protein synthesis without any effects on muscle protein degradation.42 Some studies have however not been able to find any effects of prolonged GH exposure on whole body protein turnover or albumin synthesis.39,43 A study of protein turnover in GH deficient adults have demonstrated reduced rates of protein synthesis and breakdown and subsequent normal net protein loss compared to normal controls44 in line with earlier observations of the effect of chronic GH-deficiency on protein metabolism.45
Growth hormone (GH) and intracellular STAT 5 signalling represents a very old regulatory system and, whereas insulin dominates periprandially, GH may be viewed as the primary anabolic hormone during stress and fasting. GH exerts metabolic effects both directly and through stimulation of IGF-I, insulin, and free fatty acids (FFA). When well nourished the GH-induced stimulation of IGF-I and insulin is important for tissue anabolism whereas during fasting and other catabolic states GH predominantly stimulates the release and oxidation of FFA which leads to decreased glucose and protein oxidation and preservation of LBM. The most prominent metabolic effect of GH is a marked increase in lipolysis and FFA levels. In the periprandial and postabsorptive states the effects of GH on protein metabolism are modest and include increased protein synthesis and decreased breakdown at the whole body level and in muscle together with decreased amino acid degradation/oxidation and decreased hepatic urea formation. During fasting and stress the effects of GH on protein metabolism become more pronounced; lack of GH during fasting increases protein loss and urea production rates by ≈ 50% with a similar increase in muscle protein breakdown. The importance of GH is further substantiated by the observations that adult patients with GH-deficiency are obese and have reduced LBM, and impaired physical performance and acromegaly is characterised by increased LBM and decreased fat mass.
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Administration of supraphysiologic doses of GH to athletes increases fatty acid availability and reduces oxidative protein loss particularly during exercise, and increases lean body mass. It is not known whether these effects translate to improved athletic performance, although recombinant human GH is known to be widely abused in sport. The model of acromegaly provides evidence that long-term GH excess does not result in improved performance but it is possible that a “window” exists in which the protein anabolic effects of supraphysiologic GH might be advantageous.
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The expected increase in the aging population will have a significant impact on society and the health system in the coming years and decades. Enhancing healthspan, “healthy aging”, and thus extending the time that the elderly are able to function independently is a significant task and is imperative. Age-dependent changes such as weight loss, sarcopenia and anorexia, which contribute to the development of frailty in the elderly are discussed. The role of the age-dependent decrease in growth hormone secretion in this process and the potential benefits and risks of hormonal interventions to delay, prevent or reverse frailty in the elderly are reviewed.

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^☆: Supported by an American Diabetes Association Research and Development Award to D.A.F. and National Institutes of Health Grants No. RR-125 to the Yale Clinical Research Center and RO1 DK-38578 to E.J.B. For D.A.F., data analysis and manuscript preparation were supported by a US Public Health Service Clinical Investigator Award (KO8 AR01881-01).

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Growth hormone acutely stimulates skeletal muscle but not whole-body protein synthesis in humans☆

Abstract

Am J Clin Nutr

Metab Clin Exp

Effects of human growth hormone in men over 60 years old

N Engl J Med

Growth hormone stimulates protein synthesis during hypocaloric parenteral nutrition

Ann Surg

15N tracer techniques for the differential diagnosis of dwarfism and prediction of growth hormone action in children

J Clin Endocrinol Metab

Human growth hormone prevents the catabolic side effects of prednisone in humans

J Clin Invest

Growth hormone acutely stimulates forearm muscle protein synthesis in normal humans

Am J Physiol

Effect of growth hormone on carbohydrate and lipid metabolism

Endocr Rev

Use of aromatic amino acids as monitors of protein turnover

Am J Physiol

Plasma reciprocal pool specific activity predicts that of intracellular free leucine for protein synthesis

Am J Physiol

Effect of branched-chain amino acids on muscle and whole body amino acid metabolism in man

Clin Sci

Preservation of insulin effects on glucose production and proteolysis during fasting

Am J Physiol

¹⁵N tracer techniques for the differential diagnosis of dwarfism and prediction of growth hormone action in children