The adaptive response to 3‐methylcholanthrene is altered in the liver of adrenalectomized rats
Bibliographic record
Abstract
The aryl hydrocarbon receptor (AHR) is a ligand‐activated transcription factor that mediates most effects of aromatic hydrocarbons, such as 3‐methylcholanthrene (MC). The in vivo regulation of hepatic AHR and whether changes in AHR levels affect the response to agonists are not fully understood. We discovered that the level of hepatic AHR protein was decreased in male adrenalectomized (ADX) rats 4 days after surgery. We studied the consequences of this AHR depletion by measuring expression of aromatic hydrocarbon‐responsive genes in the liver of MC‐treated ADX and SHAM‐operated rats at 6 and 54 h post‐MC. Hepatic AHR protein was depleted in ADX rats at 4 days, but not 6 days, post‐surgery. At this later time point, MC increased hepatic AHR protein in ADX but not SHAM rats. Hepatic cytochrome P450 1A1 (CYP1A1), AHR and P450 reductase (CYPRED) mRNA was induced by MC to a greater extent in SHAM versus ADX rats at 6 h. At 54 h post‐MC, induction by MC was greater in ADX versus SHAM rats for CYP1A1 and CYPRED mRNA. CYP1A1 protein levels corresponded to its mRNA. These results suggest that the adaptive response to MC in liver of ADX rats is impaired at 6 h but sustained and enhanced at 54 h relative to SHAM. Changes in the level of hepatic AHR caused by ADX affect the magnitude and duration of the response to aromatic hydrocarbons in vivo in a gene‐dependent manner. [Support: CIHR; OGS; U of Toronto; Peterborough K.M. Hunter Studentship]
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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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".