2 edition of role of glucocorticoids in the regulation of aromatic hydrocarbon receptor expression and function. found in the catalog.
role of glucocorticoids in the regulation of aromatic hydrocarbon receptor expression and function.
Kirsten Adele Bielefeld
Written in English
The aromatic hydrocarbon receptor (AHR) mediates the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). This laboratory showed previously that hepatic AHR protein levels are decreased in hypophysectomized rats, suggesting that pituitary-dependent hormones regulate AHR expression. Adrenal glucocorticoids are candidates as they have been shown to modulate AHR levels and cytochrome P450 1A inducibility. I examined effects of the glucocorticoids corticosterone (CORT) and dexamethasone (DEX) on AHR expression and function in mouse hepatoma Hepa-1 cells. CORT and DEX increased specific [3H]TCDD binding by the cytosolic AHR, and DEX stimulated a comparable elevation in AHR cytosolic immunoreactive protein and mRNA levels. The glucocorticoid receptor (GR) antagonist RU486 inhibited DEX"s effects at the ligand binding and mRNA levels. Activation of the GR was confirmed by analysis of tyrosine aminotransferase induction. This work suggests that glucocorticoids act through the GR to increase AHR expression at a pre-translational level, and may thereby influence sensitivity to AHR ligands.
|The Physical Object|
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