| 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 |
Related Documents
:
|
6101517 - Clinical course and outcome of pregnancy in twenty-five patients with pituitary microad... 873067 - Ontogenetic changes in pup-elicited maternal pituitary-adrenal activity: pup age and st... 9888597 - The regulation and role of fetal adrenal development in human pregnancy. 7277167 - Congenital neuroblastoma, neuroblastoma in situ, and the normal fetal development of th... 12505947 - A comparative study of three warming interventions to determine the most effective in m... 8784117 - Declining incidence and mortality rates of stroke in finland from 1972 to 1991. results... |
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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Pituitary adenylate cyclase-activating polypeptide regulates brain-derived neurotrophic factor exon ...
Next Document: Activator of G protein signaling 3 null mice: I. Unexpected alterations in metabolic and cardiovascu...