Glucocorticoid signaling in the cell: Expanding clinical implications to complex human behavioral and somatic disorders

George P. Chrousos, Tomoshige Kino

Research output: Chapter in Book/Report/Conference proceedingConference contribution

127 Citations (Scopus)

Abstract

Glucocorticoids contribute to the maintenance of basal and stress-related homeostasis in all higher organisms, and influence a large proportion of the expressed human genome, and their effects spare almost no organs or tissues. Glucocorticoids regulate many functions of the central nervous system, such as arousal, cognition, mood, sleep, the activity and direction of intermediary metabolism, the maintenance of a proper cardiovascular tone, the activity and quality of the immune and inflammatory reaction, including the manifestations of the sickness syndrome, and growth and reproduction. The numerous actions of glucocorticoids are mediated by a set of at least 16 glucocorticoid receptor (GR) isoforms forming homo- or hetero-dimers. The GRs consist of multifunctional domain proteins operating as ligand-dependent transcription factors that interact with many other cell signaling systems, including large and small G proteins. The presence of multiple GR monomers and homo- or hetero-dimers expressed in a cell-specific fashion at different quantities with quantitatively and qualitatively different transcriptional activities suggest that the glucocorticoid signaling system is highly stochastic. Glucocorticoids are heavily involved in human pathophysiology and influence life expectancy. Common behavioral andor somatic complex disorders, such as anxiety, depression, insomnia, chronic pain and fatigue syndromes, obesity, the metabolic syndrome, essential hypertension, diabetes type 2, atherosclerosis with its cardiovascular sequelae, and osteoporosis, as well as autoimmune inflammatory and allergic disorders, all appear to have a glucocorticoid-regulated component.

Original languageEnglish
Title of host publicationGlucocorticoids and Mood Clinical Manifestations, Risk Factors, and Molecular Mechanisms
PublisherBlackwell Publishing Inc.
Pages153-166
Number of pages14
ISBN (Print)9781573317481
DOIs
Publication statusPublished - 1 Jan 2009

Publication series

NameAnnals of the New York Academy of Sciences
Volume1179
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

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Keywords

  • CDK5
  • GR phosphorylation
  • Glucocorticoid hypersensitivity
  • Glucocorticoid resistance
  • Metabolic syndrome
  • Osteoporosis
  • Stress system

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Chrousos, G. P., & Kino, T. (2009). Glucocorticoid signaling in the cell: Expanding clinical implications to complex human behavioral and somatic disorders. In Glucocorticoids and Mood Clinical Manifestations, Risk Factors, and Molecular Mechanisms (pp. 153-166). (Annals of the New York Academy of Sciences; Vol. 1179). Blackwell Publishing Inc.. https://doi.org/10.1111/j.1749-6632.2009.04988.x