| Effects of maternal dexamethasone treatment in early pregnancy on pituitary-adrenal axis in fetal sheep. | |
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MedLine Citation:
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PMID: 19846612 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Fetal exposure to elevated levels of bioactive glucocorticoids early in gestation, as in suspected cases of congenital adrenal hyperplasia, may result in adverse neurological events. Fetal hypothalamic-pituitary-adrenal development and function may be involved. We investigated immediate and long-term effects of maternal dexamethasone (DEX) administration early in pregnancy on fetal growth and pituitary-adrenal activity in sheep. Pregnant ewes carrying singleton fetuses (total n = 119) were randomized to control (2 ml saline/ewe) or DEX-treated groups (im injections of 0.14 mg/kg ewe weight . 12 h) at 40-41 d gestation (dG). At 50, 100, 125, and 140 dG, fetal plasma and tissues were collected. DEX-exposed fetuses were lighter than controls at 100 dG (P < 0.05) but not at any other times. Fetal plasma ACTH levels and pituitary POMC and PC-1 mRNA levels were similar between groups. Fetal plasma cortisol levels were significantly reduced after DEX exposure in both male and female fetuses at 50 dG (P < 0.05), were similar at 100 and 125 dG, but were significantly higher than controls at 140 dG. At 140 dG, there was increased adrenal P450C(17) and 3beta-HSD mRNA in female fetuses and reduced expression of ACTH-R mRNA in males. Fetal hepatic CBG mRNA levels mimicked plasma cortisol patterns. DEX exposure reduced CBG only in males at 50 dG (P < 0.05). Placental mRNA levels of 11beta-HSD2 were increased after DEX in males (P < 0.05). Therefore, in sheep, early DEX may alter the developmental trajectory of the fetal hypothalamic-pituitary-adrenal axis, directly increasing fetal adrenal activation but not anterior pituitary function. In females, this effect may be attributed, in part, to increased fetal adrenal steroidogenic activity. |
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Authors:
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Thorsten Braun; Shaofu Li; Deborah M Sloboda; Wei Li; Melanie C Audette; Timothy J M Moss; Stephen G Matthews; Graeme Polglase; Ilias Nitsos; John P Newnham; John R G Challis |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-10-21 |
Journal Detail:
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Title: Endocrinology Volume: 150 ISSN: 1945-7170 ISO Abbreviation: Endocrinology Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-25 Completed Date: 2010-01-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
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Languages: eng Pagination: 5466-77 Citation Subset: AIM; IM |
Affiliation:
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Department of Physiology and Obstetrics and Gynecology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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11-beta-Hydroxysteroid Dehydrogenase Type 2
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genetics Adrenal Glands / drug effects, embryology, metabolism Adrenocorticotropic Hormone / blood Animals Dexamethasone / administration & dosage, pharmacology* Female Fetal Blood / metabolism Fetal Development / drug effects* Fetus / drug effects*, metabolism Gene Expression Regulation, Developmental / drug effects Gestational Age Glucocorticoids / administration & dosage, pharmacology In Situ Hybridization Male Multienzyme Complexes / genetics Pituitary Gland / drug effects, embryology, metabolism Pituitary-Adrenal System / drug effects*, embryology Placenta / drug effects, metabolism Pregnancy Pro-Opiomelanocortin / genetics Progesterone Reductase / genetics Random Allocation Reverse Transcriptase Polymerase Chain Reaction Sex Factors Sheep Steroid 17-alpha-Hydroxylase / genetics Steroid Isomerases / genetics |
| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; 0/Glucocorticoids; 0/Multienzyme Complexes; 50-02-2/Dexamethasone; 66796-54-1/Pro-Opiomelanocortin; 9002-60-2/Adrenocorticotropic Hormone; EC 1.1.1.145/Progesterone Reductase; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 2; EC 1.14.99.9/Steroid 17-alpha-Hydroxylase; EC 5.3.3.-/Steroid Isomerases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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