Regulation of NADPH‐cytochrome P450 oxidoreductase by glucocorticoids in rat liver
Bibliographic record
Abstract
NADPH‐Cytochrome P450 oxidoreductase (POR) is the obligate electron donor for all microsomal P450s, key catalysts of endobiotic and xenobiotic metabolism. Adrenalectomized rats show decreased hepatic POR activity that is rescued by cortisone. Dexamethasone (DEX), a synthetic glucocorticoid known to activate both the glucocorticoid receptor (GR) and the pregnane X receptor (PXR), increases hepatic levels of POR mRNA in rats and POR protein in wild‐type and Gr‐ null mice. To study the roles of GR and PXR in POR regulation, we treated male rats with the GR‐selective agonist triamcinolone acetonide (TA), the PXR‐selective agonist pregnenolone‐16α‐carbonitrile (PCN), and several doses of DEX. At 6 h after dosing, PCN caused a 3‐fold induction of POR mRNA and a trend for increased POR mRNA levels was seen in response to TA. Neither PCN nor TA alone affected POR protein levels or cytochrome c reduction activity. A low dose of DEX (1 mg/kg), shown to activate GR but not PXR, caused a 3‐fold induction of POR mRNA at 6 h, whereas a high dose of DEX (50 mg/kg), shown to activate both GR and PXR, increased POR mRNA levels by nearly 5‐fold at 6 h and 4‐fold at 24 h. POR protein levels and cytochrome c reduction activity were increased at 24 h after the high dose of DEX. Both GR and PXR may contribute to the rat hepatic POR mRNA induction, but activation of either receptor alone seems insufficient to elevate POR protein and activity. [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) | 0.000 | 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) | 0.001 | 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".