Document Detail


Effects of maternal dexamethasone treatment in early pregnancy on pituitary-adrenal axis in fetal sheep.
MedLine Citation:
PMID:  19846612     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-21
Journal Detail:
Title:  Endocrinology     Volume:  150     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-25     Completed Date:  2010-01-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5466-77     Citation Subset:  AIM; IM    
Affiliation:
Department of Physiology and Obstetrics and Gynecology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
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MeSH Terms
Descriptor/Qualifier:
11-beta-Hydroxysteroid Dehydrogenase Type 2 / 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:
//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
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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