Dexamethasone-induced apoptosis of mouse thymocytes: prevention by native 7alpha-hydroxysteroids
| Autor: | R Morfin, V Chmielewski, F Drupt |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Immunology Dehydroepiandrosterone Apoptosis Thymus Gland Epiandrosterone Biology In Vitro Techniques Androsterone Dexamethasone Mice Internal medicine Mole polycyclic compounds medicine Immunology and Allergy Animals Carbon Radioisotopes skin and connective tissue diseases Cells Cultured Hydroxysteroids Cell Biology Organ Size Flow Cytometry Phenotype Mice Inbred C57BL Thymocyte Endocrinology Pregnenolone human activities hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Immunology and cell biology. 78(3) |
| ISSN: | 0818-9641 |
| Popis: | Dehydroepiandrosterone (DHEA) has been shown to decrease the dexamethasone (DEX)-induced apoptosis of thymocytes and to be one of the native 3beta-hydroxysteroids extensively 7alpha-hydroxylated in thymus. This led us to question whether DHEA or 7alpha-hydroxy-DHEA is responsible for the decrease in DEX-induced apoptosis of thymocytes and whether this property is shared with other native 3beta-hydroxysteroids and their 7alpha-hydroxylated metabolites. Treatment of mice with DHEA or 7alpha-hydroxy-DHEA prior to DEX led to a smaller decrease in thymus weight than with DEX alone and to a disappearance of the DEX-induced changes in thymocyte phenotypes. Thymocyte apoptosis induced by DEX treatment was significantly lowered in DHEA- and 7alpha-hydroxy-DHEA-treated thymi, even after 18 h culture with additional 10-6 mol/L DEX. Extensive apoptosis of thymocytes cultured with 10-7 mol/L DEX was brought back to control levels when 10-5 mol/L 7alpha-hydroxy-DHEA or 10-5 mol/L 7alpha-hydroxy-epiandrosterone was added. After use of DHEA and epiandrosterone or pregnenolone, less significant and no significant changes were obtained, respectively. These findings imply that the 7alpha-hydroxylation of 3beta-hydroxysteroids may be a prerequisite for an exquisite regulation of the thymocyte-positive selection driven by the glucocorticoids produced in thymic epithelial cells. |
| Databáze: | OpenAIRE |
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