Rat hepatic cytochrome P450 oxidoreductase is up‐regulated by low dose dexamethasone and down‐regulated by adrenalectomy
Bibliographic record
Abstract
Microsomal cytochrome P450 (CYP) enzyme activity requires cytochrome P450 oxidoreductase (POR). We studied rat hepatic POR after adrenalectomy (ADX) since some CYP activities are decreased by ADX. The effects of ADX or glucocorticoids on POR are not clear. Male ADX or SHAM‐ADX rats were treated with dexamethasone (DEX) once 6 h before euthanasia, 4 days post‐ADX (acute), or once daily in the third week post‐ADX (subacute). A DEX time‐course study was also performed in intact rats. Hepatic POR was measured by quantitative RT‐PCR and by immunoblot. Hepatic POR protein but not mRNA was decreased at 4 days and 3 weeks post‐ADX. Subacute DEX dosing (1 mg/kg) returned hepatic POR protein in ADX rats to SHAM levels; a single dose (1.5 mg/kg) showed a similar trend. DEX induced hepatic POR mRNA in SHAM and ADX rats in both dosing regimens. DEX is a selective glucocorticoid receptor (GR) agonist at low doses but activates the pregnane X receptor (PXR) at higher doses. CYP3A23 , a PXR target gene, was measured to determine whether DEX activated the PXR. Hepatic CYP3A23 mRNA was not induced up to 27 h post‐DEX in the time‐course but showed a modest 30% increase with subacute DEX dosing in SHAM rats. In this study, DEX induced POR mRNA and protein but not CYP3A23 mRNA, suggesting a role for GR in POR regulation. Further studies are needed to determine how DEX at low doses acts to induce the obligate redox partner for all microsomal CYPs. [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 | 0.001 | 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) | 0.002 | 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".