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Glucocorticoid action networks and complex psychiatric and/or somatic disorders
George P Chrousos1, Tomoshige Kino
1First Department of Pediatrics, Athens University Medical School, 11527 Athens, Greece. chrousog@mail.nih.gov
Stress (Amsterdam, Netherlands)
|May 22, 2007
Summary
Glucocorticoids are vital for maintaining bodily balance and are implicated in numerous diseases. Understanding their role via glucocorticoid receptors (GRs) is key to human health and longevity.
Area of Science:
- Endocrinology
- Molecular Biology
- Human Pathophysiology
Background:
- Glucocorticoids are essential hormones regulating homeostasis and influencing a vast portion of the human genome.
- Their effects span multiple organ systems, impacting the central nervous system, metabolism, cardiovascular function, immunity, growth, and reproduction.
Purpose of the Study:
- To elucidate the fundamental role of glucocorticoids in maintaining homeostasis and their involvement in human pathophysiology.
- To explore the mechanisms of glucocorticoid action through various glucocorticoid receptor (GR) isoforms.
Main Methods:
- Review and synthesis of existing evidence on glucocorticoid function and receptor interactions.
- Analysis of the stochastic nature of the glucocorticoid signaling system due to multiple GR isoforms and dimerization.
Main Results:
- Glucocorticoid actions are mediated by at least 16 GR isoforms, forming dimers that function as ligand-dependent transcription factors.
- The glucocorticoid signaling system exhibits stochastic properties due to cell-specific expression and varying activities of GR monomers and dimers.
Conclusions:
- Glucocorticoids play a significant role in human pathophysiology and influence life expectancy.
- Numerous complex disorders, including psychiatric, metabolic, cardiovascular, and autoimmune diseases, appear to have a glucocorticoid component.
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