Genomic and nongenomic effects of glucocorticoids

@article{Stahn2008GenomicAN,
  title={Genomic and nongenomic effects of glucocorticoids},
  author={Cindy Stahn and F. Buttgereit},
  journal={Nature Clinical Practice Rheumatology},
  year={2008},
  volume={4},
  pages={525-533}
}
The strong anti-inflammatory and immunosuppressive effects of glucocorticoids are mediated primarily by the cytosolic glucocorticoid receptors. These receptors are members of the steroid hormone receptor family, a superfamily of ligand-inducible transcription factors, and exert genomic effects that can result in increased expression of regulatory—including anti-inflammatory—proteins (transactivation), or decreased production of proinflammatory proteins (transrepression). Transactivation is… Expand
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References

SHOWING 1-10 OF 77 REFERENCES
Molecular mechanisms of glucocorticoid action and selective glucocorticoid receptor agonists
TLDR
The crux of the matter should be the design of qualitatively new drugs, such as selective glucocorticoid receptor agonists (SEGRAs). Expand
Selective glucocorticoid receptor agonists (SEGRAs): Novel ligands with an improved therapeutic index
TLDR
A high medical need exists for drugs as effective as glucocorticoids but with a reduced side effect profile, and selective GR agonists that promote the negative regulatory action of the receptor with reduced positive regulatory function should show an improved therapeutic index. Expand
Insight into the molecular mechanisms of glucocorticoid receptor action promotes identification of novel ligands with an improved therapeutic index
TLDR
Increases in the therapeutic action of glucocorticoid receptor ligands that promote the negative regulatory action of the receptor with reduced positive regulatory function should show improved therapeutic potential. Expand
Novel insights into mechanisms of glucocorticoid action and the development of new glucocorticoid receptor ligands
TLDR
Novel GC receptor ligands, such as selective glucocorticoid receptor agonists (SEGRAs), are discussed, which might optimize genomic GC effects as they preferentially induce transrepression with little or no transactivating activity. Expand
Rapid glucocorticoid effects on immune cells
TLDR
The first evidence has now been found to suggest a physiological expression of membrane-bound glucocorticoid receptors on human cells, whereas in humans this had previously only been demonstrated on lymphoma cells. Expand
The effects of non-genomic glucocorticoid mechanisms on bodily functions and the central neural system. A critical evaluation of findings
TLDR
The discovery of non-genomic mechanisms of glucocorticoids is a major breakthrough in stress research, and further insights into these mechanisms may open novel approaches for the therapy of various diseases. Expand
Glucocorticoid action and novel mechanisms of steroid resistance: role of glucocorticoid receptor-interacting proteins for glucocorticoid responsiveness.
  • A. Wikström
  • Biology, Medicine
  • The Journal of endocrinology
  • 2003
TLDR
It is suggested that a closer study of GR-interacting proteins may shed new light on mechanisms determining glucocorticoid sensitivity and a proteomic-based method to study GR- interacting proteins will be described in brief. Expand
Antiinflammatory glucocorticoid receptor ligand with reduced side effects exhibits an altered protein–protein interaction profile
TLDR
A compound, LGD5552, is presented that binds the receptor efficiently and strongly represses inflammatory gene expression and may offer a safer alternative to steroidal glucocorticoids in the treatment of inflammatory disease. Expand
Non-genomic glucocorticoid effects to provide the basis for new drug developments
TLDR
The current knowledge on non-genomic glucocorticoid actions is described and why these actions are considered to be of therapeutic relevance are discussed. Expand
Mechanisms involved in the side effects of glucocorticoids.
TLDR
This review summarizes the current knowledge of the most important GC-mediated side effects from a clinical to a molecular perspective and should be helpful in predicting the potential advantages of selective GR agonists in comparison to classical GCs. Expand
...
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2
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4
5
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