Evidence map›Paper›PMID 19920132›Full record

ArticleThe Journal of biological chemistry2010

Estrogen-mediated regulation of Igf1 transcription and uterine growth involves direct binding of estrogen receptor alpha to estrogen-responsive elements.

Sylvia C Hewitt, Yin Li, Leping Li, Kenneth S Korach

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 9% 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

72 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.

  1. Pooled it
  2. Pregnancy damps thermoregulatory rhythms across timescales through neural estrogen signaling in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Sex-Specific Regulation of β-Secretase: A Novel Estrogen Response Element (ERE)-Dependent Mechanism in Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Insulin signaling is an essential regulator of endometrial proliferation and implantation in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  19. Endometrial biomarkers in premenopausal women with obesity: an at-risk cohort.American journal of obstetrics and gynecology · 2021
    Article
  20. Review

12 more citing papers are in PubMed but not listed here.

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 3 institutions in 1 country.

Sylvia C HewittReceptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. curtiss@niehs.nih.gov
Yin Li
Leping Li
Kenneth S Korach
National Institutes of Health · USNational Institute of Environmental Health Sciences · USReproductive Science Center · US

Funding

Chemical Receptor Interactions In Reproduction And Hormonal ToxicityZIAES070065 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI KORACH, KENNETH S · 2009 to 2019
$29.6M
BioinformaticsZIAES101765 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI LI, LEPING · 2009 to 2025
$21.0M
Chemical Receptor Interactions Reproduction/HormonalZ01ES070065 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI KORACH, KENNETH S · 1985 to 2008
$5.0M
BioinformaticsZ01ES101765 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI LI, LEPING · 2004 to 2008
$1.1M
Intramural NIH HHS Z01 ES070065Intramural NIH HHS Z01 ES101765
6 · The paper itself

Abstract

Estrogen enables uterine proliferation, which depends on synthesis of the IGF1 growth factor. This proliferation and IGF1 synthesis requires the estrogen receptor (ER), which binds directly to target DNA sequences (estrogen-responsive elements or EREs), or interacts with other transcription factors, such as AP1, to impact transcription. We observe neither uterine growth nor an increase in Igf1 transcript in a mouse with a DNA-binding mutated ER alpha (KIKO), indicating that both Igf1 regulation and uterine proliferation require the DNA binding function of the ER. We identified several potential EREs in the Igf1 gene, and chromatin immunoprecipitation analysis revealed ER alpha binding to these EREs in wild type but not KIKO chromatin. STAT5 is also reported to regulate Igf1; uterine Stat5a transcript is increased by estradiol (E(2)), but not in KIKO or alpha ERKO uteri, indicating ER alpha- and ERE-dependent regulation. ER alpha binds to a potential Stat5a ERE. We hypothesize that E(2) increases Stat5a transcript through ERE binding; that ER alpha, either alone or together with STAT5, then acts to increase Igf1 transcription; and that the resulting lack of IGF1 impairs KIKO uterine growth. Treatment with exogenous IGF1, alone or in combination with E(2), induces proliferation in wild type but not KIKO uteri, indicating that IGF1 replacement does not rescue the KIKO proliferative response. Together, these observations suggest in contrast to previous in vitro studies of IGF-1 regulation involving AP1 motifs that direct ER alpha-DNA interaction is required to increase Igf1 transcription. Additionally, full ER alpha function is needed to mediate other cellular signals of the growth factor for uterine growth.

Indexed as

AnimalsCell DivisionEpithelial CellsEstrogen Receptor alphaEstrogensFemaleGene Expression RegulationHumansInsulin-Like Growth Factor IIntronsMaleMiceMice, KnockoutPromoter Regions, GeneticResponse ElementsSTAT5 Transcription FactorEstrogen Receptor alphaEstrogensinsulin-like growth factor-1, mouseInsulin-Like Growth Factor IStat5a protein, mouseSTAT5 Transcription Factor

Identifiers

PMID19920132
PMCPMC2807324
OpenAlexW2081882809

What OpenQuestion holds

Textmetadata
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.