The effect of cortisone on protein breakdown and synthesis in rat skeletal muscle

Exercise-training might be a logical method to reverse muscle atrophy and weakness in patients treated with glucocorticoids. The purpose of the present investigation was to establish whether a treatment with low dose prednisone (10±2.9 mg/d) modulates the effect of a moderate strength type isokinetic training during 7 wk (21 sessions of 20 min) on "muscle efficiency" (power output/muscle mass) and on concomitant changes in ultrastructure of the thigh muscle measured by quantitative electron-microscopic morphometry. Training caused a similar increase in "muscle efficiency" in patients on prednisone (a = 9) as in normal volunteers (a = 9). In normal subjects the increase in muscle efficiency was associated with an increase in sarcoplasm, whereas in patients on prednisone the functional improvement was associated with an increase in sarcoplasm, capillaries, and mitochondria content. Thus, a therapy with low dose prednisone does not abrogate training-induced improvement of muscle efficiency but modulates the ultrastructural response of the muscle to the trinng.

Section: Discussionmentioning

confidence: 99%

Impact of physical training on the ultrastructure of midthigh muscle in normal subjects and in patients treated with glucocorticoids.

Horber¹,

Hoopeler²,

Scheidegger³

et al. 1987

“…The proteolytic effect ofpharmacologic amounts ofglucocorticoids on skeletal muscle is evidenced by increases in (a) efflux of amino acids from incubated rat muscle (2-4); (b) plasma amino acid concentrations in eviscerated animal preparations (5,6); (c) plasma urea nitrogen (2); (d) muscle dipeptidase activity (7); and (e) 3-methylhistidine excretion (8). In contrast, no significant increase in protein degradation was observed in rat muscle following several days of high dose in vivo corticosterone exposure (9)(10)(11). Inhibition of protein synthesis also has been invoked to explain the protein catabolic state induced by steroids on the basis of decreased incorporation of amino acids into rat muscle following glucocorticoid treatment (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Increased proteolysis. An effect of increases in plasma cortisol within the physiologic range.

Simmons¹,

Miles²,

Gerich³

et al. 1984

274

117

As bstract. Prolonged exposure to glucocorticoids in pharmacologic amounts results in muscle wasting, but whether changes in plasma cortisol within the physiologic range affect amino acid and protein metabolism in man has not been determined. To determine whether a physiologic increase in plasma cortisol increases proteolysis and the de novo synthesis ofalanine, seven normal subjects were studied on two occasions during an 8-h infusion ofeither hydrocortisone sodium succinate (2 1g

“…doses of glucocorticoids. Other investigators (14,15) failed to show increased protein breakdown after glucocorticoids even though they observed depression of protein synthesis. In this study, the 70% increase in the rate of appearance of leucine in plasma represents a minimum estimate, since intracellular specific activity may be lower than plasma.…”

Section: Discussionmentioning

confidence: 96%

“…It is well known that glucocorticoid hormones promote the net release of amino acids from muscle by decreasing protein synthesis (14,15). Their effect on protein breakdown, however, remains controversial.…”

Section: Discussionmentioning

confidence: 99%

Leupeptin Inhibits Adrenocorticotropic Hormone-induced Protein Breakdown in the Conscious Dog

McCallister¹,

Lacy²,

Williams³

et al. 1983

A B S T R A C T To elucidate the role of proteinase inhibitors in the regulation of protein breakdown in vivo, we measured the effect of leupeptin on the rate of appearance of leucine in the plasma compartment in overnight-fasted conscious dogs. Two groups of dogs were studied. The control group (I) received saline infusion, and the experimental group (II) was rendered hypercatabolic with daily administration of adrenocorticotropic hormone (ACTH) (500 U/d) for 4 d.ACTH treatment increased plasma cortisol from 2±0.4 to 17±2 Asg/dl (P < 0.005). It raised plasma leucine levels (jsmol/liter) from 123±6 in I to 206±5in II (P < 0.01) and its rate of appearance into the plasma compartment (micromoles per kilogram per minute) from 3.1±0.1 in I to 4.6±0.3 in II (P < 0.01). Whole blood alanine concentration (micromoles per liter) increased by 50% (from 387±31 to 577±53, P < 0.01) and whole blood glutamine concentration (micromoles per liter) increased from 653±51 to 917±93 (P < 0.01). Leupeptin infusion in the ACTHtreated group significantly decreased both the concentration of plasma leucine and its rate of appearance. Blood glutamine declined by 30% (P < 0.05) after leupeptin, but no effect on blood alanine was observed.Leupeptin had no effect on the saline control group. These data indicate that leupeptin decreases the accelerated rate of protein breakdown induced by cortisol excess. The fact that it did not affect protein degAddress reprint requests to Dr. Abumrad.