Dimerization of the Glucocorticoid Receptor and Its Importance in (Patho)physiology: A Primer
Abstract
1. Introduction
1.1. Glucocorticoids
1.2. Glucocorticoid Receptor: Structure and Function
2. Ligand-Induced GR Homodimer Formation
2.1. The DBD Interface
2.2. The LBD Interface
3. GR Dimer Mutations
4. GR Dimer and Monomer Transcriptional Regulation
5. Alternative Partners for Dimer Formation
6. Role of GR Complex Formation in SIRS and Sepsis
6.1. SIRS and Sepsis
6.2. Anti-Inflammatory Genes Induced by GR Complex Formation
6.3. Pro-Inflammatory Genes Suppressed by GR Complex Formation
6.4. Hemodynamic and Metabolic Parameters Controlled by GR Complex Formation
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Process | Effect in GRdim/dim Mutant | References |
---|---|---|
Resolution of inflammation | ||
Antigen- and G6PI-induced arthritis | DEX protection lost | [50] |
Serum transfer-induced arthritis | DEX protection lost | [51] |
Contact hypersensitivity | DEX protection lost | [52] |
PMA-induced irritative skin inflammation | DEX protection intact | [53,54] |
Experimental autoimmune encephalomyelitis | DEX protection intact | [55] |
Allergic airway inflammation | DEX protection lost | [56] |
Graft- vs host disease | Increased mortality | [57] |
TNF-induced SIRS | Increased mortality + DEX protection lost | [58,59] |
LPS-induced SIRS | Increased mortality + DEX protection lost | [60,61,62,63] |
CLP-induced septic shock | Increased mortality | [64,65] |
Side effects | ||
Hyperglycemia | Pred effect reduced | [66,67] |
Osteoporosis | Pred/DEX effect intact | [68,69,70] |
Skeletal muscle atrophy | DEX effect intact | [71] |
Wound repair | Wound repair reduced | [72] |
Gastroparesis and gastric acid secretion | DEX effect lost | [73] |
Ocular hypertension leading to glaucoma | DEX effect lost | [74] |
Glucocorticoid resistance | DEX effect lost | [75] |
Cellular processes | ||
Adipogenesis | No adipogenesis | [76] |
Apoptosis | DEX effect lost | [46,77] |
Proliferation | Proliferation reduced | [46] |
Spatial memory | Spatial memory reduced | [78] |
Cognitive function under stress condition | CORT effect reduced | [79] |
Weight control | Body weight increased | [80] |
Activation HPA axis in 6% hypoxia | Activation of HPA axis reduced | [81] |
Trauma-induced fracture healing | Protected | [82] |
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Timmermans, S.; Vandewalle, J.; Libert, C. Dimerization of the Glucocorticoid Receptor and Its Importance in (Patho)physiology: A Primer. Cells 2022, 11, 683. https://doi.org/10.3390/cells11040683
Timmermans S, Vandewalle J, Libert C. Dimerization of the Glucocorticoid Receptor and Its Importance in (Patho)physiology: A Primer. Cells. 2022; 11(4):683. https://doi.org/10.3390/cells11040683
Chicago/Turabian StyleTimmermans, Steven, Jolien Vandewalle, and Claude Libert. 2022. "Dimerization of the Glucocorticoid Receptor and Its Importance in (Patho)physiology: A Primer" Cells 11, no. 4: 683. https://doi.org/10.3390/cells11040683
APA StyleTimmermans, S., Vandewalle, J., & Libert, C. (2022). Dimerization of the Glucocorticoid Receptor and Its Importance in (Patho)physiology: A Primer. Cells, 11(4), 683. https://doi.org/10.3390/cells11040683