Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction

Ann N Y Acad Sci. 2012 Jul:1261:55-63. doi: 10.1111/j.1749-6632.2012.06633.x.

Abstract

Enhanced susceptibility to inflammatory and autoimmune disease can be related to impairments in HPA axis activity and associated hypocortisolism, or to glucocorticoid resistance resulting from impairments in local factors affecting glucocorticoid availability and function, including the glucocorticoid receptor (GR). The enhanced inflammation and hypercortisolism that typically characterize stress-related illnesses, such as depression, metabolic syndrome, cardiovascular disease, or osteoporosis, may also be related to increased glucocorticoid resistance. This review focuses on impaired GR function as a molecular mechanism of glucocorticoid resistance. Both genetic and environmental factors can contribute to impaired GR function. The evidence that glucocorticoid resistance can be environmentally induced has important implications for management of stress-related inflammatory illnesses and underscores the importance of prevention and management of chronic stress. The simultaneous assessment of neural, endocrine, and immune biomarkers through various noninvasive methods will also be discussed.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Corticosterone / immunology
  • Corticosterone / metabolism
  • Cushing Syndrome / metabolism
  • Cushing Syndrome / physiopathology
  • Depression / genetics
  • Depression / metabolism
  • Depression / physiopathology
  • Glucocorticoids / immunology
  • Glucocorticoids / metabolism*
  • Humans
  • Hypothalamo-Hypophyseal System / metabolism*
  • Hypothalamo-Hypophyseal System / physiopathology
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Inflammation / physiopathology
  • Metabolic Diseases / physiopathology
  • Mice
  • Neuroimmunomodulation / physiology
  • Osteoporosis / metabolism
  • Osteoporosis / physiopathology
  • Pituitary-Adrenal System / metabolism*
  • Pituitary-Adrenal System / physiopathology
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / immunology
  • Receptors, Glucocorticoid / metabolism*
  • Stress, Psychological / genetics
  • Stress, Psychological / metabolism
  • Stress, Psychological / physiopathology

Substances

  • Biomarkers
  • Glucocorticoids
  • Receptors, Glucocorticoid
  • Corticosterone