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This Article Full Text Full Text (PDF) All Versions of this Article: 286/2/E311    most recent 00158.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Fletcher, A. J. W. Articles by Giussani, D. A. Search for Related Content PubMed PubMed Citation Articles by Fletcher, A. J. W. Articles by Giussani, D. A.

Antenatal glucocorticoids reset the level of baseline and hypoxemia-induced pituitary-adrenal activity in the sheep fetus during late gestation

Andrew J. W. Fletcher,¹ Xiao Hong Ma,^2, Wen X. Wu,² Peter W. Nathanielsz,² Hugh H. G. McGarrigle,³ Abigail L. Fowden,¹ and Dino A. Giussani^{1, 4}

¹Department of Physiology, University of Cambridge, Cambridge CB2 3EG; ³Department of Obstetrics & Gynaecology, University College London, London WC1E 6HX, United Kingdom; and ²Laboratory for Pregnancy & Newborn Research, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853

Submitted 11 April 2003 ; accepted in final form 7 October 2003

This study examined the effects of dexamethasone treatment on basal hypothalamo-pituitary-adrenal (HPA) axis function and HPA responses to subsequent acute hypoxemia in the ovine fetus during late gestation. Between 117 and 120 days (term: 145 days), 12 fetal sheep and their mothers were catheterized under halothane anesthesia. From 124 days, 6 fetuses were continuously infused intravenously with dexamethasone (1.80 ± 0.15 µg·kg^–1·h^–1 in 0.9% saline at 0.5 ml/h) for 48 h, while the remaining 6 fetuses received saline at the same rate. Two days after infusion, when dexamethasone had cleared from the fetal circulation, acute hypoxemia was induced in both groups for 1 h by reducing the maternal fraction of inspired O₂. Fetal dexamethasone treatment transiently lowered fetal basal plasma cortisol, but not ACTH, concentrations. However, 2 days after treatment, fetal basal plasma cortisol concentration was elevated without changes in basal ACTH concentration. Despite elevated basal plasma cortisol concentration, the ACTH response to acute hypoxemia was enhanced, and the increment in plasma cortisol levels was maintained, in dexamethasone-treated fetuses. Correlation of fetal plasma ACTH and cortisol concentrations indicated enhanced cortisol output without a change in adrenocortical sensitivity. The enhancements in basal cortisol concentration and the HPA axis responses to acute hypoxemia after dexamethasone treatment were associated with reductions in pituitary and adrenal glucocorticoid receptor mRNA contents, which persisted at 3–4 days after the end of treatment. These data show that prenatal glucocorticoids alter the basal set point of the HPA axis and enhance HPA axis responses to acute stress in the ovine fetus during late gestation.

dexamethasone; hypoxemia

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