In vivo endocrine regulation of rat hepatic aryl hydrocarbon receptor expression and function
Bibliographic record
Abstract
The aryl hydrocarbon receptor (AHR) is a ligand‐activated transcription factor that mediates the effects of aromatic hydrocarbons (AHs) such as 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin (TCDD). AHR‐mediated transcriptional regulation has been extensively studied, as exemplified by the prototypical induction of cytochrome P450 1A1 (CYP1A1) following AH exposure. However, the in vivo regulation of the expression of the hepatic AHR itself is poorly understood and the impact of changes in AHR expression on AH responsiveness is unclear. With respect to hormonal regulation of the AHR, our laboratory showed that hypophysectomy decreases hepatic AHR protein and TCDD‐binding in male rats. This suggested that the AHR is positively regulated by pituitary‐dependent factors in vivo . We initially focused on adrenal glucocorticoids (GCs) as candidate pituitary‐dependent hormones in this response, since GCs can increase AHR expression and AH responsiveness in vitro . We hypothesized that GCs elevate AHR expression in rat liver, sensitizing rats to the diverse effects of AHs. Male rats were either adrenalectomized (ADX) or underwent sham surgery, and then rats were treated with either dexamethasone (DEX) or vehicle. Neither ADX nor DEX treatment had a significant effect on hepatic AHR expression, as assessed at the mRNA, protein and TCDD‐binding levels. Thus, GCs are not important regulators of rat hepatic AHR expression in vivo . Other pituitary‐dependent regulators of AHR expression and function will be studied in vivo to better understand the hormonal regulation of the AHR and how different hormonal states influence sensitivity to AHs. [Support: NSERC, 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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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) | 0.003 | 0.001 |
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".