Metabolic functions of glucocorticoid receptor in skeletal muscle

Mol Cell Endocrinol. 2013 Nov 5;380(1-2):79-88. doi: 10.1016/j.mce.2013.03.003. Epub 2013 Mar 21.

Abstract

Glucocorticoids (GCs) exert key metabolic influences on skeletal muscle. GCs increase protein degradation and decrease protein synthesis. The released amino acids are mobilized from skeletal muscle to liver, where they serve as substrates for hepatic gluconeogenesis. This metabolic response is critical for mammals' survival under stressful conditions, such as fasting and starvation. GCs suppress insulin-stimulated glucose uptake and utilization and glycogen synthesis, and play a permissive role for catecholamine-induced glycogenolysis, thus preserving the level of circulating glucose, the major energy source for the brain. However, chronic or excess exposure of GCs can induce muscle atrophy and insulin resistance. GCs convey their signal mainly through the intracellular glucocorticoid receptor (GR). While GR can act through different mechanisms, one of its major actions is to regulate the transcription of its primary target genes through genomic glucocorticoid response elements (GREs) by directly binding to DNA or tethering onto other DNA-binding transcription factors. These GR primary targets trigger physiological and pathological responses of GCs. Much progress has been made to understand how GCs regulate protein and glucose metabolism. In this review, we will discuss how GR primary target genes confer metabolic functions of GCs, and the mechanisms governing the transcriptional regulation of these targets. Comprehending these processes not only contributes to the fundamental understanding of mammalian physiology, but also will provide invaluable insight for improved GC therapeutics.

Keywords: Glucocorticoid receptor; Glucocorticoids; Glucose metabolism; Insulin; Protein metabolism; Skeletal muscle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carbohydrate Metabolism
  • Gene Expression Regulation
  • Glucocorticoids / physiology*
  • Humans
  • Insulin / physiology
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / metabolism*
  • Protein Biosynthesis
  • Receptors, Glucocorticoid / physiology*
  • Response Elements

Substances

  • Glucocorticoids
  • Insulin
  • Muscle Proteins
  • Receptors, Glucocorticoid