Regulation of the Human Cholesterol 7α-Hydroxylase Gene (CYP7A1) by Thyroid Hormone in Transgenic Mice
Bibliographic record
Abstract
Thyroid hormones exert significant changes in the metabolism of bile acids. However, in humans, the effect of thyroid hormone on cholesterol 7alpha-hydroxylase (cyp7a), the rate- controlling enzyme in the classical bile acid biosynthetic pathway, remains poorly understood and has been difficult to study directly in vivo. Previous studies from our laboratory have shown that the activity of the human cholesterol 7alpha-hydroxylase gene promoter is repressed by T(3) in cultured cells. Accordingly, we hypothesized that T(3) would negatively regulate human CYP7A1 gene expression in vivo. We tested this hypothesis by inducing hypo- and hyperthyroidism in transgenic mice expressing the human CYP7A1 gene. Hypothyroidism did not affect the abundance of human cyp7a mRNA in transgenic mice. In hyperthyroid male mice, human cyp7a mRNA abundance was decreased. No significant change in cyp7a mRNA abundance was observed in hyperthyroid female mice. Gender differences in the amount of cholesterol and bile acids in gallbladder bile were also observed. The data indicate that thyroid hormone can repress the human CYP7A1 gene in transgenic mice, but this effect is dependent on gender in this in vivo model.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".