From the Guidelines
The main effect of glucocorticoids on protein metabolism is catabolic, leading to increased protein breakdown and decreased protein synthesis, as evidenced by the loss of muscle protein and behavioral changes of starvation at the same time as storage of excess energy as fat 1.
Key Effects of Glucocorticoids on Protein Metabolism
- Increased protein breakdown: Glucocorticoids stimulate proteolysis in skeletal muscle and other tissues, leading to the release of amino acids into the bloodstream.
- Decreased protein synthesis: Glucocorticoids inhibit protein synthesis by interfering with mRNA translation and reducing amino acid uptake into muscle cells.
- Loss of muscle protein: The catabolic effect of glucocorticoids results in the loss of muscle protein, leading to muscle wasting and steroid myopathy.
- Behavioral changes: Glucocorticoids lead to behavioral changes of starvation, including increased appetite and failure to trigger satiety, despite the storage of excess energy as fat.
Clinical Implications
The protein catabolic effect of glucocorticoids has significant clinical implications, including:
- Muscle wasting and steroid myopathy
- Skin thinning
- Osteoporosis
- Increased risk of fractures, particularly vertebral fractures
- Reversible risk factor for glucocorticoid-induced osteoporosis (GIOP) if treatment is terminated 2, 3
Importance of Dose and Duration
The severity of the protein catabolic effects of glucocorticoids depends on the dose, potency, and duration of treatment, with higher doses and longer durations causing more pronounced protein catabolism 2, 3. Therefore, it is essential to carefully consider the benefits and risks of glucocorticoid treatment and to monitor patients for signs of protein catabolism and other adverse effects.
From the Research
Effects of Glucocorticoids on Protein Metabolism
- Glucocorticoids can cause muscle atrophy, but their effect on muscle protein metabolism in humans is complex 4, 5.
- Research suggests that glucocorticoids can regulate protein metabolism in skeletal muscle, producing a catabolic effect that is opposite to that of insulin 5.
- However, a study found that short-term moderate dose of prednisone had no effect on whole-body or leg muscle protein metabolism or muscle function 4.
- Glucocorticoids are known to impair protein synthesis signaling, myotube formation, and muscle-specific protein expression, but IGF-I can synergistically stimulate myotube fusion and myofibrillar protein expression in the presence of glucocorticoids 6.
- Chronic administration of glucocorticosteroids can have significant catabolic effects, including inhibiting protein synthesis and increasing protein breakdown, but growth hormone and IGF-I may decrease these catabolic effects 7.
- Acute and chronic low-dose glucocorticoids can have different effects on protein metabolism, with acute administration stimulating protein oxidation, but chronic administration showing no significant difference in protein metabolism compared to normal subjects 8.
Key Findings
- Glucocorticoids can cause muscle atrophy and regulate protein metabolism in skeletal muscle 5.
- IGF-I can synergistically stimulate myotube fusion and myofibrillar protein expression in the presence of glucocorticoids 6.
- Growth hormone and IGF-I may decrease the catabolic effects of chronic steroid use 7.
- Acute and chronic low-dose glucocorticoids can have different effects on protein metabolism 8.