Role of glucocorticoids in the molecular regulation of muscle wasting

Abstract

Muscle wasting in various catabolic conditions is, at least in part, regulated by glucocorticoids. The role of glucocorticoids in muscle wasting is complex and reflects regulation at the molecular level of multiple mechanisms influencing both synthesis and degradation of muscle proteins.

Dexamethasone downregulates caveolin-1 causing muscle atrophy via inhibited insulin signaling

“…To examine the role of caveolins in glucocorticoidinduced muscle atrophy, we used DEX-treated C2C12 myotubes as an in vitro model (Menconi et al 2007, Schakman et al 2008. C2C12 myotubes were treated with DEX at several concentrations (100 nM, 1 mM, 10 mM, and 100 mM) for various periods.…”

Gene expression changes in subcutaneous adipose tissue due to Cushing's disease

“…Muscle wasting is a well recognized adverse event of excess glucocorticoids caused by both increased muscle proteolysis and decreased protein synthesis (Deng et al 2004, Menconi et al 2007. Exposure of rats to glucocorticoids activates the muscle ubiquitin-proteasome system (Wing & Goldberg 1993, Price et al 1994, increasing muscle expression of proteases (cathepsins B and D, calpain) and components of the ubiquitin-proteasome pathway (Dardevet et al 1995) along with the inhibition of muscle protein synthesis (Long et al 2001).…”

Type I Diabetes and the Role of Inflammatory-Related Cellular Signaling

“…Insulinopenia, together with increased glucocorticoids have been shown to enhance muscle protein degradation through increased ubiquitin conjugation to proteins, proteolytic activity, and ubiquitin pathway component mRNA transcription (Price, Bailey et al 1996;Bailey, Wang et al 1999). Elevated levels of glucocorticoids have also been found to contribute to skeletal muscle atrophy through increased expression of ubiquitin pathway proteins, transcription factors CCAAT/enhancer-binding protein  and  and Forkhead box O (Foxo), and nuclear cofactor p300/histone acetyl transferase (Menconi, Fareed et al 2007). In addition to catabolic factors, glucocorticoids contribute to muscle atrophy through inhibition of anabolic factors, insulin signaling, and stimulation of protein synthesis Hu, Wang et al 2009).…”

“…Catabolic doses of glucocorticoids have been implicated in a number of muscle wasting diseases including T1DM where increases in corticosterone production have been observed (Bailey, Wang et al 1999;Menconi, Fareed et al 2007). Circulating increases in TNF- and IL-1 can stimulate the pituitary-adrenal axis to increase secretion of corticosterone (Gwosdow, Kumar et al 1990;Hall-Angeras, Angeras et al 1990).…”

“…T1DM-associated milieu disrupts tissue protein homeostasis and induces a net negative protein balance, particularly in skeletal muscle. Patients with T1DM often display profound skeletal muscle atrophy, which results in muscle weakness, fatigue, delayed recovery after illness, and has been linked with increased morbidity and mortality (Gordon, Serino et al;Menconi, Fareed et al 2007). Skeletal muscle atrophy associated with T1DM results from the upregulation of numerous catabolic factors, which increase protein degradation and decrease processes of protein synthesis.…”