Document Detail


Inhibition of brain prostaglandin endoperoxide synthase-2 prevents the preparturient increase in fetal adrenocorticotropin secretion in the sheep fetus.
MedLine Citation:
PMID:  18450957     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Maturation of the fetal hypothalamus-pituitary-adrenal axis is critical for the timely somatic development of the fetus and readiness for birth. Recently, we proposed that prostaglandin generation within the fetal central nervous system is critical for the modulation of hypotension-induced fetal ACTH secretion. The present study was designed to test the hypothesis that the preparturient increase in fetal ACTH secretion is dependent upon fetal central nervous system prostaglandin synthesis mediated by the activity of prostaglandin endoperoxide synthase (PGHS)-2 (cyclooxygenase-2) in the fetal brain. We performed two studies in chronically catheterized fetal sheep. In the first study, we infused nimesulide or vehicle intracerebroventricularly (i.c.v) into singleton fetal sheep and collected blood samples until spontaneous parturition. Nimesulide significantly delayed parturition, and inhibited fetal ACTH and proopiomelanocortin secretion but did not prevent the preparturient increase in fetal plasma cortisol concentration. In the second study, we used twin fetuses. One fetus received intracerebroventricular nimesulide and the other intracerebroventricular vehicle. Nimesulide reduced brain tissue concentrations of prostaglandin estradiol, while not affecting plasma prostaglandin E(2) concentrations, demonstrating an action restricted to the fetal brain. Nimesulide reduced PGHS-2 mRNA and increased PGHS-2 protein, while not altering PGHS-1 mRNA or protein in most brain regions, suggesting an effect of the inhibitor on PGHS-2 turnover and relative specificity for PGHS-2 in vivo. We conclude that the preparturient increase in fetal ACTH and proopiomelanocortin is dependent upon the activity of PGHS-2 in the fetal brain. However, we also conclude that the timing of parturition is not solely dependent upon ACTH in this species.
Authors:
Jason Gersting; Christine E Schaub; Maureen Keller-Wood; Charles E Wood
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-05-01
Journal Detail:
Title:  Endocrinology     Volume:  149     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-23     Completed Date:  2008-08-26     Revised Date:  2013-03-27    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4128-36     Citation Subset:  AIM; IM    
Affiliation:
Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Florida 32610-0274, USA.
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MeSH Terms
Descriptor/Qualifier:
Adrenocorticotropic Hormone / secretion*
Animals
Brain / drug effects*,  embryology*,  enzymology,  secretion
Cyclooxygenase 2 / metabolism
Cyclooxygenase 2 Inhibitors / administration & dosage,  pharmacology*
Female
Fetus / drug effects,  metabolism
Gene Expression Regulation, Enzymologic / drug effects
Gestational Age
Hypothalamo-Hypophyseal System / drug effects,  metabolism,  physiology
Injections, Intraventricular
Parturition / drug effects,  metabolism*
Pituitary-Adrenal System / drug effects,  metabolism,  physiology
Pregnancy
Pregnancy, Multiple / metabolism
Pro-Opiomelanocortin / secretion
Sheep
Sulfonamides / administration & dosage,  pharmacology
Twins
Grant Support
ID/Acronym/Agency:
HD33053/HD/NICHD NIH HHS; HD42135/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Cyclooxygenase 2 Inhibitors; 0/Sulfonamides; 51803-78-2/nimesulide; 66796-54-1/Pro-Opiomelanocortin; 9002-60-2/Adrenocorticotropic Hormone; EC 1.14.99.1/Cyclooxygenase 2
Comments/Corrections

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