Document Detail


Estrogen receptor-β and fetoplacental endothelial prostanoid biosynthesis: a link to clinically demonstrated fetal growth restriction.
MedLine Citation:
PMID:  21832119     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: Fetal growth restriction (FGR) due to placental dysfunction impacts short- and long-term neonatal outcomes. Abnormal umbilical artery Doppler velocimetry indicating elevated fetoplacental vascular resistance has been associated with fetal morbidity and mortality. Estrogen receptors are regulators of vasomotor tone, and fetoplacental endothelium expresses estrogen receptor-β (ESR2) as its sole estrogen receptor.
OBJECTIVE: Our objective was to elucidate the mechanism whereby ESR2 regulates placental villous endothelial cell prostanoid biosynthesis.
DESIGN AND PARTICIPANTS: We conducted immunohistochemical analysis of human placental specimens and studies of primary fetoplacental endothelial cells isolated from subjects with uncomplicated pregnancies.
MAIN OUTCOME MEASURES: We evaluated in vivo levels of ESR2 and cyclooxygenase-2 (PTGS2) in villous endothelial cells from fetuses with or without FGR and/or abnormal umbilical artery Doppler indices and in vitro effects of ESR2 on prostanoid biosynthetic gene expression.
RESULTS: ESR2 and PTGS2 expression were significantly higher within subjects with FGR with abnormal umbilical artery Doppler indices in comparison with controls (P < 0.01). ESR2 knockdown led to decreased cyclooxygenase-1 (PTGS1), PTGS2, prostaglandin F synthase (AKR1C3), and increased prostacyclin synthase (PTGIS), with opposing results found after ESR2 overexpression (P < 0.05). ESR2 mediates prostaglandin H2 substrate availability and, in the setting of differential regulation of AKR1C3 and PTGIS, altered the balance between vasodilatory and vasoconstricting prostanoid production.
CONCLUSIONS: Higher ESR2 expression in the placental vasculature of FGR subjects with abnormal blood flow is associated with an endothelial cell phenotype that preferentially produces vasoconstrictive prostanoids. Endothelial ESR2 appears to be a master regulator of prostanoid biosynthesis and contributes to high-resistance fetoplacental blood flow, thereby increasing morbidity and mortality associated with FGR.
Authors:
Emily J Su; Linda Ernst; Nadine Abdallah; Robert Chatterton; Hong Xin; Diana Monsivais; John Coon; Serdar E Bulun
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-08-10
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  96     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-06     Completed Date:  2011-11-18     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E1558-67     Citation Subset:  AIM; IM    
Affiliation:
Northwestern University Feinberg School of Medicine, 250 East Superior Street, Suite 05-2175, Chicago, Illinois 60611, USA. e-su@northwestern.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Blotting, Western
Databases, Factual
Endothelial Cells / metabolism
Endothelium / metabolism*
Estradiol / pharmacology
Estrogen Receptor beta / biosynthesis,  genetics,  metabolism*
Female
Fetal Growth Retardation / genetics,  metabolism*
Fetus / blood supply,  metabolism*
Humans
Immunohistochemistry
Male
Muscle Tonus / physiology
Placenta / metabolism*
Pregnancy
Prostaglandin-Endoperoxide Synthases / metabolism
Prostaglandins / biosynthesis*
RNA Interference
Regional Blood Flow / physiology
Reverse Transcriptase Polymerase Chain Reaction
Vasoconstriction / physiology
Vasodilation / physiology
Grant Support
ID/Acronym/Agency:
K08-HDHD061654//PHS HHS
Chemical
Reg. No./Substance:
0/Estrogen Receptor beta; 0/Prostaglandins; 50-28-2/Estradiol; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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