Evidence map›Paper›PMID 27170438›Full record

ArticleBiology of reproduction2016

Identification of Differential ER-Alpha Versus ER-Beta Mediated Activation of eNOS in Ovine Uterine Artery Endothelial Cells.

Mayra B Pastore, Saira Talwar, Meghan R Conley, Ronald R Magness

Open access · hybridAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Biology of reproduction, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.7field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Effects of dietary soy content on cerebral artery function and behavior in ovariectomized female mice.American journal of physiology. Heart and circulatory physiology · 2024
    Article
  4. Review
  5. Article
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  10. Impaired estrogen signaling underlies regulatory T cell loss-of-function in the chronically inflamed intestine.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  11. Estrogen Receptors and Estrogen-Induced Uterine Vasodilation in Pregnancy.International journal of molecular sciences · 2020
    Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Effect of Oxidative Stress on the Estrogen-NOS-NO-KOxidative medicine and cellular longevity · 2019
    Review
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Mayra B PastoreDepartment of Obstetrics & Gynecology Perinatal Research Labs, University of Wisconsin-Madison, Madison, Wisconsin.
Saira TalwarDepartment of Obstetrics & Gynecology Perinatal Research Labs, University of Wisconsin-Madison, Madison, Wisconsin.
Meghan R ConleyDepartment of Obstetrics & Gynecology Perinatal Research Labs, University of Wisconsin-Madison, Madison, Wisconsin.
Ronald R MagnessDepartment of Obstetrics & Gynecology Perinatal Research Labs, University of Wisconsin-Madison, Madison, Wisconsin Department of Animal Sciences, University of Wisconsin-Madison, Madison, Wisconsin Department of Pediatrics, University of Wisconsin-Madison, Madison, Wisconsin University of South Florida Perinatal Research Center, Tampa, Florida rmagness@health.usf.edu.
University of Wisconsin–Madison · US

Funding

Unified Cellular and Molecular CoreP01HD038843 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI BIRD, IAN M. · 2001 to 2017
$14.4M
Endocrinology-Reproductive Physiology Training GrantT32HD041921 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI BIRD, IAN M. · 2004 to 2022
$3.0M
ENDOTHELIUM-DERIVED VASODILATORS IN PREGNANCYR01HL049210 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI MAGNESS, RONALD R · 1993 to 2011
$2.6M
Physiologic Cardiovascular & Uterine eNOS Responses:Role of Endogenous EstrogenR01HL087144 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI MAGNESS, RONALD R · 2007 to 2010
$1.8M
Endothelial Function in a Model of IUGR Induced by Uterine Space RestrictionR01HL117341 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI MAGNESS, RONALD R · 2014 to 2017
$1.8M
NHLBI NIH HHS R01 HL049210NHLBI NIH HHS R01 HL087144NHLBI NIH HHS R01 HL117341NICHD NIH HHS P01 HD038843NICHD NIH HHS T32 HD041921
6 · The paper itself

Abstract

Endothelial nitric oxide (NO) production is partly responsible for maintenance of uterine vasodilatation during physiologic states of high circulating estrogen levels, e.g., pregnancy. Although 3%-5% of estrogen receptors (ER-alpha/beta) localize to the endothelial plasmalemma, these receptors are responsible for the nongenomic vasodilator responses. Estradiol induces endothelial NO synthase (eNOS) activation to increase NO production; however, it is unknown if eNOS regulation is dependent on both ERs. We hypothesize that ER-alpha and/or ER-beta are capable of changing eNOS phosphorylation and increasing NO production in uterine artery endothelial cells (UAECs). UAECs were 1) treated with vehicle or increasing concentrations (0.1-100 nM) or timed treatments (0-30 min) of estradiol and 2) pretreated with the inhibitors ICI 182,780 (nonspecific ER), 1,3-Bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP; ER-alpha specific), or 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP; ER-beta specific) followed by estradiol to analyze the changes in eNOS stimulatory (Ser1177)eNOS and (Ser635)eNOS versus inhibitory (Thr495)eNOS via Western blot analysis. UAECs were also pretreated with MPP, PHTPP, or MPP + PHTTP followed by estradiol or treated with the agonists estradiol, 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol, 2,3-bis(4-hydroxyphenyl)-propionitrile, or ATP to quantify total NOx levels (NO2+NO3). Estrogen and ER-alpha activation induced an increase in (Ser1177)eNOS and (Ser635)eNOS, a decrease in (Thr495)eNOS, and an increase in NOx levels. In contrast, ER-beta activation only reduced (Thr495)eNOS without changes in (Ser1177)eNOS or (Ser635)eNOS. However, ER-beta activation increased NOx levels. Lastly, the antagonism of both receptors induced a reduction in basal and stimulated NOx levels in UAECs. These data demonstrate that 1) eNOS phosphorylation changes occur via ER-alpha- and ER-beta-dependent mechanisms and 2) ER-alpha and ER-beta can both increase NO levels independently from each other.

Indexed as

AnimalsEndothelial CellsEndothelium, VascularEstrogen Receptor alphaEstrogen Receptor betaFemaleNitric OxideNitric Oxide Synthase Type IIIPhosphorylationPregnancySheepUterine ArteryEstrogen Receptor alphaEstrogen Receptor betaNitric OxideNitric Oxide Synthase Type IIINOS3 protein, humanendothelial cellseNOSERαERβestradiolestrogenestrogen receptornitric oxideNOpregnancyuterine vasculature

Identifiers

PMID27170438
PMCPMC4946807
OpenAlexW2357544716

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.