11β-Hydroxysteroid dehydrogenase type 2 in zebrafish brain: a functional role in hypothalamus-pituitary-interrenal axis regulation
Why this work is in the frame
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Bibliographic record
Abstract
The type 2, 11β-hydroxysteroid dehydrogenase (Hsd11b2) converts active glucocorticoids to their inactive derivatives (e.g. cortisol to cortisone). In most vertebrates, Hsd11b2 is essential for conferring aldosterone-specific actions in mineralocorticoid target tissues and for protecting glucocorticoid-sensitive tissues during stress. However, teleosts do not synthesize aldosterone, and the function of Hsd11b2 is poorly defined. The distribution of Hsd11b2 in nonmammalian brain is also largely unexplored. We tested the hypothesis that modulation of brain Hsd11b2 activity is involved in stressor-mediated cortisol regulation in zebrafish (Danio rerio). In adult zebrafish, the stress effect on Hsd11b2 expression in the brain was tested using acute air exposure followed by recovery over a 24-h period. hsd11b2 transcripts were found in nearly all peripheral tissues examined, and a spatial map of its mRNA abundance in unstressed zebrafish brain revealed extensive distribution. Stressor exposure increased the conversion of (3)H-cortisol to (3)H-cortisone indicating enhanced Hsd11b2 activity in zebrafish brain. Promoter analysis of zebrafish hsd11b2 gene revealed putative sites for cortisol-mediated transcriptional regulation of this gene. Furthermore, inhibition of Hsd11b2 activity by 18β-glycyrrhetinic acid resulted in elevated whole-body cortisol levels and preoptic area mRNA abundance of corticotropin-releasing factor and mineralocorticoid receptor. Taken together, our results underscore an important role for brain Hsd11b2 involvement in the negative feedback regulation of cortisol poststress in zebrafish.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it