The 11-ketosteroid 11-ketodexamethasone is a glucocorticoid receptor agonist
| Autor: | Andrea R. Nawrocki, Alex Odermatt, Brigitte M. Frey, Michael E. Baker, Steven P. Tam, Felix J. Frey, Alexandre G Rebuffat |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Transcriptional Activation
Agonist endocrine system medicine.medical_specialty Hydrocortisone medicine.drug_class Active Transport Cell Nucleus Biochemistry Dexamethasone Cell Line Transactivation Receptors Glucocorticoid Endocrinology Glucocorticoid receptor Mineralocorticoid receptor 11β-hydroxysteroid dehydrogenase type 1 Internal medicine polycyclic compounds medicine Animals Humans Receptor Molecular Biology Binding Sites biology Chemistry Ketosteroids Kinetics biology.protein Cortisone hormones hormone substitutes and hormone antagonists Glucocorticoid Protein Binding medicine.drug |
| Zdroj: | Molecular and Cellular Endocrinology. 214:27-37 |
| ISSN: | 0303-7207 |
| DOI: | 10.1016/j.mce.2003.11.027 |
| Popis: | Dexamethasone (Dex) is a potent and long-acting glucocorticoid in terms of anti-inflammatory activity without substantial sodium retaining effect. Here, we examine the ability of the 11beta-hydroxyglucocorticoids Dex and cortisol and their 11-keto forms 11-ketodexamethasone (11-ketoDex) and cortisone to bind to glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) and to mediate nuclear translocation and transactivation of a reporter-gene. Unlike cortisone, the 11-ketosteroid 11-ketoDex acts as a potent GR agonist, comparable to Dex and cortisol. Transactivation of MR by Dex or 11-ketoDex was weak or undetectable, despite efficient binding and induction of nuclear translocation. 11beta-HSD2 protects MR and GR from inappropriate occupation by cortisol; it is, however, unable to prevent activation of GR by 11-ketoDex. The finding that 11-ketoDex is a specific GR agonist may explain the potent glucocorticoid effect of Dex in tissues expressing 11beta-HSD2 including kidney and colon and also in certain tumor cells. |
| Databáze: | OpenAIRE |
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