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 most recent study in 2020 1. This catabolic effect is characterized by the stimulation of proteolysis in skeletal muscle and other tissues, resulting in the release of amino acids into the bloodstream. These amino acids are then transported to the liver, where they serve as substrates for gluconeogenesis, the process of generating new glucose.
- Key aspects of glucocorticoid-induced catabolism include:
- Increased protein breakdown in skeletal muscle and other tissues
- Decreased protein synthesis in peripheral tissues due to interference with amino acid uptake and reduction of mRNA translation
- Release of amino acids into the bloodstream, which are then used for gluconeogenesis in the liver
- The severity of these catabolic effects depends on the dose, potency, and duration of glucocorticoid treatment, with higher doses and longer durations causing more pronounced protein catabolism, as noted in studies such as 1 and 1.
- This protein catabolic effect explains many of the adverse effects seen with chronic glucocorticoid therapy, including muscle wasting (steroid myopathy), skin thinning, and osteoporosis, highlighting the importance of careful consideration and monitoring in the clinical use of glucocorticoids.
From the Research
Main Effect of Glucocorticoids on Protein Metabolism
- Glucocorticoids are known to regulate protein metabolism in skeletal muscle, producing a catabolic effect that is opposite to that of insulin 2.
- The catabolic effect of glucocorticoids can lead to muscle atrophy, particularly in catabolic diseases such as sepsis, starvation, and cancer cachexia, where endogenous glucocorticoids are elevated 2.
- Exogenous glucocorticoids, often given to treat inflammatory conditions, can also result in muscle atrophy due to their catabolic effects on muscle protein metabolism 2.
Mechanisms of Glucocorticoid-Induced Catabolism
- Glucocorticoids can inhibit protein synthesis and increase protein breakdown at the skeletal muscle and whole-body level, impairing growth hormone secretion and action 3.
- The catabolic effects of glucocorticoids may be counteracted by growth hormone and insulin-like growth factor I, which are potent protein-anabolic and growth-promoting agents 3.
- Glucocorticoids can stimulate protein oxidation, particularly after acute administration, but this effect may not persist with chronic administration due to metabolic adaptation 4.
Effects of Glucocorticoids on Muscle Protein Metabolism
- Short-term moderate doses of prednisone may not affect whole-body or leg muscle protein metabolism, but can affect glucose metabolism 5.
- Chronic administration of low-dose glucocorticoids may not induce sustained catabolism, with no significant differences in protein metabolism compared to normal subjects 4.
- Glucocorticoids can differentially regulate degradation of muscle regulatory factors, such as MyoD and Id1, by N-terminal ubiquitination to promote muscle protein catabolism 6.