The Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Corticotrophin-Releasing Hormone, Arginine Vasopressin, and Pro-opiomelanocortin mRNA Levels in the Hypothalamus of the Cynomolgus Monkey
Bibliographic record
Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental contaminant that has profound deleterious effects on development and reproduction. TCDD may act at one or more levels to alter the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. The objective of this study was to investigate whether TCDD modulates neuroendocrine systems by altering gene expression of arginine vasopressin (AVP), corticotrophin-releasing hormone (CRH), or pro-opiomelanocortin (POMC), which are important neuroregulators of the HPA and HPG axes. Four groups of female cynomolgus monkeys (Macaca fascicularis) were administered daily oral doses of gelatin capsule containing TCDD (0, 1, 5, or 25 ng/kg body weight) mixed with glucose 5 days a week for 1 year. At the end of the dosing period, animals were euthanized and brains were harvested. CRH, AVP, and POMC mRNA levels were semiquantified by in situ hybridization histochemistry on 30-microm coronal sections of the brain. Blood collected on the day of euthanasia was assayed for cortisol and progesterone. CRH mRNA levels in the paraventricular nucleus (PVN) were significantly increased by the 2 higher TCDD doses (5 and 25 ng/kg/day) compared to controls (p < 0.05). There was a trend towards increased AVP mRNA levels in both the supraoptic nucleus (SON) and PVN. No effect of TCDD on POMC was observed. Cortisol levels were significantly increased in TCDD-exposed animals. Progesterone concentrations and menstruation data indicated that TCDD did not interfere with ovulation. We conclude that TCDD stimulated the HPA axis by a central effect involving CRH, but had no effect on the HPG axis at the doses tested.
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How this classification was reachedexpand
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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".