Glucocorticoids and muscle catabolism

Abstract

Glucocorticoids inhibit protein synthesis and stimulate protein degradation in skeletal muscle and are an important factor in the development of muscle atrophy in various catabolic conditions. Glucocorticoid-stimulated muscle protein breakdown is primarily caused by ubiquitin-proteasome-dependent proteolysis although calcium-dependent protein degradation may also be involved. In certain catabolic conditions, including sepsis, an interaction between glucocorticoids and proinflammatory cytokines is important for the stimulation of muscle protein breakdown.

Effects of energy restriction on activity of the hypothalamo-pituitary-adrenal axis in obese humans and rodents: implications for diet-induced changes in body composition

“…Glucocorticoids, through their interaction with insulin, promote the differentiation of pre-adipocytes into mature fat cells as well as stimulating lipoprotein lipase activity, which facilitates fat accumulation, particularly in the abdomen [33,74,75]. High levels of glucocorticoids inhibit myocyte synthesis and promote breakdown through stimulating protein catabolism pathways [33,76]. This process is further accelerated in the absence of insulin [77].…”

“…This process is further accelerated in the absence of insulin [77]. This would most likely be seen in the fasting scenario, where insulin levels are reduced and the body needs to convert stored energy to useable energy [76]. Additionally, the reduced circulating insulin concentrations typically observed during weight loss interventions in obese individuals might therefore be expected to enhance the catabolic effects of glucocorticoids on myocytes.…”

“…Longer-term use (more than 60 days) of oral glucocorticoids is associated with self-reported weight gain in over 60% of patients, including those on lower doses (e.g., 10 mg/day prednisone for 6 months), and weight gain is the most commonly reported adverse event in patients taking glucocorticoids [61]. Additionally, people with Cushing ' s syndrome, associated with primary hypercortisolism, exhibit hyperphagia, weight gain, visceral obesity and muscle wasting [19,76,79], further demonstrating a primary role of increased glucocorticoid action in the propensity to store fat (particularly central fat) at the expense of lean tissues.…”

Corticosteroid effects on ventilator-induced diaphragm dysfunction in anesthetized rats depend on the dose administered

“…In skeletal muscle, glucocorticoids decrease the rate of muscle protein synthesis and increase the rate of muscle proteolysis [4]. The stimulatory effect of corticosteroids on muscle proteolysis results from the activation of the proteolytic systems such as the ubiquitin-proteasome system (UPS), the lysosomal system, the calcium-dependent calpain system and the caspase-3 system [5,6]. …”

The Pathophysiologic Response to Severe Burn Injury.

“…Stress hormones such as glucocorticoids have been described as one of the major hormones responsible for proteolysis and catabolism. [57][58][59][60] Glucocorticoid levels are markedly increased postburn, and therefore, a hypothetical approach to attenuate protein breakdown and hypermetabolism would be to block cortisol production. We are currently conducting a prospective randomized controlled trial to block cortisol production using ketoconazole.…”