Glucocorticoids enhance aryl hydrocarbon receptor expression and function in mouse hepatoma cells
Bibliographic record
Abstract
The aryl hydrocarbon receptor (AHR) is a ligand‐activated transcription factor that mediates most biological responses to 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin (TCDD). Although the AHR's role in control of drug metabolism and endocrine disruption are partly understood, we know little about the regulation of the AHR itself by endocrine factors. Our work with hypophysectomized rats suggested that hepatic AHR protein level is positively regulated by pituitary‐dependent factors. One current hypothesis is that adrenal glucocorticoids elevate AHR expression and enhance responsiveness to AHR agonists. Dexamethasone (DEX) at concentrations that activate the glucocorticoid receptor (GR) increased AHR mRNA, protein and TCDD‐binding by approximately 50% in Hepa‐1 mouse hepatoma cells. This response was blocked by the GR antagonist RU486, suggesting GR involvement. This small magnitude increase in AHR levels was functionally significant; pre‐treatment of Hepa‐1 cells with DEX caused a 75% increase in the maximum induction of an AHR‐activated luciferase reporter by TCDD. A new luciferase reporter under control of the proximal 2.5‐kb of the mouse AHR 5′‐flank was induced approximately 2‐fold by DEX but only with co‐transfection of a mouse GR expression plasmid. The molecular mechanisms and in vivo relevance of this pathway for endocrine control of AHR expression and function are being explored. [Support: CIHR]
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".