Evidence map›Paper›PMID 23296142›Full record

ArticleSteroids2013

Membrane-initiated estradiol signaling in immortalized hypothalamic N-38 neurons.

Reymundo Dominguez, Phoebe Dewing, John Kuo, Paul Micevych

Open access · greenAbstract read
In one paragraph

Article in Steroids, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
5.2field-weighted citation impact, top 6% 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

19 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
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  9. Actions of Steroids: New Neurotransmitters.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016
    Review
  10. Review
  11. Article
  12. Review
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  14. Review
  15. Article
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  17. Review
  18. Review
  19. Neurosteroids, trigger of the LH surge.The Journal of steroid biochemistry and molecular biology · 2012
    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.

Reymundo DominguezLaboratory of Neuroendocrinology of the Brain Research Institute, Departments of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1763, United States. reymundd@usc.edu
Phoebe Dewing
John Kuo
Paul Micevych
University of California, Los Angeles · US

Funding

SEX STEROID ACTIVATION OF OPIOID CIRCUITS IN THE CNSR01DA013185 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MICEVYCH, PAUL E · 2001 to 2016
$5.0M
Neuroendocrinology, Sex Differences, and ReproductionT32HD007228 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARNOLD, ARTHUR P · 1985 to 2015
$3.9M
The Regulation of Plasma Membrane Estrogen Receptor-a Levels by EndocytosisF32NS079064 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DOMINGUEZ, REYMUNDO · 2012 to 2012
$53k
NICHD NIH HHS T32 HD007228NIDA NIH HHS DA013185NIDA NIH HHS R01 DA013185NINDS NIH HHS F32 NS079064NINDS NIH HHS NS079064
6 · The paper itself

Abstract

Regulation of sexual reproduction by estradiol involves the activation of estrogen receptors (ERs) in the hypothalamus. Of the two classical ERs involved in reproduction, ERα appears to be the critical isoform. The role of ERα in reproduction has been found to involve a nuclear ERα that induces a genomic mechanism of action. More recently, a plasma membrane ERα has been shown to trigger signaling pathways involved in reproduction. Mechanisms underlying membrane-initiated estradiol signaling are emerging, including evidence that activation of plasma membrane ERα involves receptor trafficking. The present study examined the insertion of ERα into the plasma membrane of N-38 neurons, an immortalized murine hypothalamic cell line. We identified, using western blotting and PCR that N-38 neurons express full-length 66kDa ERα and a 52kDa ERα spliced variant missing the fourth exon - ERαΔ4. Using surface biotinylation, we observed that treatment of N-38 neurons with estradiol or with a membrane impermeant estradiol elevated plasma membrane ERα protein levels, indicating that membrane signaling increased receptor insertion into the cell membrane. Insertion of ERα was blocked by the ER antagonist ICI 182,780 or with the protein kinase C (PKC) pathway inhibitor bisindolylmaleimide (BIS). Downstream membrane-initiated signaling was confirmed by estradiol activation of PKC-theta (PKCθ) and the release of intracellular calcium. These results indicate that membrane ERα levels in N-38 neurons are dynamically autoregulated by estradiol.

Indexed as

Signal TransductionAnimalsCell MembraneEstradiolEstrogen Receptor alphaHypothalamusMiceNeuronsRNA, MessengerEstradiolEstrogen Receptor alphaRNA, Messenger

Identifiers

PMID23296142
PMCPMC3636190
OpenAlexW1979134590

What OpenQuestion holds

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LicenceTDM
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.