- Title
- Effect of antalarmin, a novel corticotrophin-releasing hormone antagonist, on the dynamic function of the ovine fetal hypothalamo-pituitary-adrenal axis
- Creator
- Young, I. Ross; Chan, E. Cheng; Smith, Roger; Chrousos, George P.; Veldhuis, Johannes D.; Canny, Benedict J.
- Relation
- Neuroendocrinology: International Journal for Basic and Clinical Studies on Neuroendocrine Relationships Vol. 76, Issue 1, p. 47-54
- Publisher Link
- http://dx.doi.org/10.1159/000063683
- Publisher
- Karger
- Resource Type
- journal article
- Date
- 2002
- Description
- 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 E| 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 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.
- Subject
- corticotropin; corticotropin-releasing hormone; adrenal steroids; fetal neuroendocrinology; ovine; antalarmin
- Identifier
- uon:965
- Identifier
- http://hdl.handle.net/1959.13/26602
- Identifier
- ISSN:1423-0194
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