Effect of Antalarmin, a Novel Corticotropin-Releasing Hormone Antagonist, on the Dynamic Function of the Preterm Ovine Fetal Hypothalamo-Pituitary-Adrenal Axis
| Autor: | Johannes D. Veldhuis, Benedict J. Canny, E. Cheng Chan, I. Ross Young, George P. Chrousos, Roger Smith |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Cortisol secretion
endocrine system medicine.medical_specialty Hydrocortisone Corticotropin-Releasing Hormone Endocrinology Diabetes and Metabolism Hypothalamus Gestational Age Fetal Hypoxia Cellular and Molecular Neuroscience Basal (phylogenetics) Corticotropin-releasing hormone Endocrinology Adrenocorticotropic Hormone Pregnancy Internal medicine Adrenal Glands medicine Animals Pyrroles Antalarmin Secretion Fetus Sheep Endocrine and Autonomic Systems business.industry Gestational age Oxygen Kinetics Pyrimidines Pituitary Gland Cosyntropin Female business hormones hormone substitutes and hormone antagonists Corticotropin-releasing hormone antagonist medicine.drug |
| Zdroj: | Neuroendocrinology. 76:47-54 |
| ISSN: | 1423-0194 0028-3835 |
| DOI: | 10.1159/000063683 |
| Popis: | 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 ACTH1–24 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. |
| Databáze: | OpenAIRE |
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