Effect of Antalarmin, a Novel Corticotropin-Releasing Hormone Antagonist, on the Dynamic Function of the Preterm Ovine Fetal Hypothalamo-Pituitary-Adrenal Axis
Bibliographic record
Abstract
This study describes the effect of antalarmin on basal and stimulated activity of the hypothalamo-pituitary-adrenal (HPA) axis function in the late gestation ovine fetus. Fetuses received antalarmin (15 mg/h i.v.) or vehicle (cremophor El 50% in ethanol) from day 130 gestational age. Antalarmin infusion did not significantly affect immunoreactive corticotropin (ir-ACTH) concentrations, although there was a tendency for ir-ACTH to be lower and cortisol concentrations were lower in the antalarmin-treated fetuses (p < 0.01). The ir-ACTH response to corticotropin-releasing hormone (CRH) challenge was attenuated (p < 0.05) in the antalarmin-treated fetuses, but neither antalarmin- nor vehicle-treated fetuses had significant cortisol responses to CRH. The ir-ACTH response to hypoxia was diminished (p < 0.05) in the antalarmin-treated fetuses while the cortisol responses of antalarmin- and vehicle-treated fetuses were indistinguishable. Deconvolution analysis revealed no effect of antalarmin treatment on ir-ACTH secretory dynamics. In contrast, antalarmin decreased (p < 0.05) basal, mean and integrated cortisol. The plasma cortisol responses of antalarmin- and vehicle-treated fetuses to exogenous ACTH(1-24) were indistinguishable. These data indicate that, while antalarmin inhibits CRH- and stress-induced ir-ACTH secretion, basal ir-ACTH secretion may be less affected by antalarmin treatment. Paradoxically, cortisol secretion is impaired by antalarmin infusion, although adrenal responsiveness to ACTH is not impaired. These results confirm a role for CRH in stress-induced ACTH secretion in the ovine fetus, though its role in the regulation of basal ACTH and cortisol secretion is unclear.
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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 | 0.000 |
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 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".