Evidence map›Paper›PMID 24033289›Full record

ArticleJournal of neurochemistry2013

Estrogen receptor-β regulates human tryptophan hydroxylase-2 through an estrogen response element in the 5' untranslated region.

Ryoko Hiroi, Robert J Handa

Open access · bronzeAbstract read
In one paragraph

Article in Journal of neurochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.9field-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

34 citing papers in PubMed, 68 citations in OpenAlex.

  1. Dorsal raphe tau pathology disrupts sleep-wake orchestration and sleep architecture in a sex-specific manner.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  2. Article
  3. Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. ProcessedHeliyon · 2024
    Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Environmental Pollution to Blame for Depressive Disorder?International journal of environmental research and public health · 2022
    Article
  18. Review
  19. Review
  20. 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

2 authors at 1 institution in 1 country.

Ryoko HiroiDepartment of Basic Medical Sciences, University of Arizona College of Medicine - Phoenix, Phoenix, Arizona, USA.
Robert J Handa
University of Arizona · US

Funding

SEX DIFFERENCES IN HYPOTHALAMO-PITUITARY-ADRENAL AXISR01NS039951 · NINDS · UNIVERSITY OF ARIZONA · PI HANDA, ROBERT J · 2001 to 2013
$4.3M
Regulation of the Tryptophan Hydroxylase-2 Promoter by EstrogenF32MH093145 · NIMH · UNIVERSITY OF ARIZONA · PI HIROI, RYOKO · 2011 to 2013
$166k
NIMH NIH HHS F32 MH093145NIMH NIH HHS F32-MH093145NINDS NIH HHS R01 NS039951NINDS NIH HHS R01-NS039951
6 · The paper itself

Abstract

In the dorsal raphe nucleus, 17β-estradiol (E2) increases the expression of the brain-specific, rate-limiting enzyme for serotonin biosynthesis, tryptophan hydroxylase-2 (Tph2). Although estrogen receptor beta (ERβ) has been localized to Tph2 neurons, little is known about the transcriptional regulation of the Tph2 gene by estrogen. Since the ERβ agonist, diarylpropionitrile (DPN) also increases Tph2 expression, we tested the hypothesis that E2 regulates the Tph2 promoter through direct interactions with ERβ. A serotonergic cell line, B14, which endogenously expresses ERβ was transiently transfected with a fragment of the human TPH2 5'-untranslated region (5'-UTR) cloned into a luciferase reporter vector (TPH2-luc). Treatment with E2 or DPN caused a dose-dependent increase of TPH2-luc activity. In contrast, E2 conjugated to bovine serum albumin, which is cell membrane impermeable, had no effect on TPH2-luc activity. An estrogen receptor (ER) antagonist blocked E2 or DPN-induced TPH2-luc activity suggesting a classical ER mechanism. In silico analysis revealed an estrogen-response element (ERE) half-site located within the TPH2 5'-UTR. Deletion and site-directed mutation of this site abolished ligand-induced TPH2-luc activity. These results support the concept that there is a direct and functional interaction between E2:ERβ and the ERE half-site of the TPH2 promoter to regulate Tph2 expression. We illustrate a direct regulation of the TPH2 transcription by estradiol and ERβ via a newly identified ERE half-site within the TPH2 promoter: (i) Estradiol- or an ERβ agonist-induced TPH2 transcription was blocked by an ER antagonist, while (ii) membrane impermeable form of estradiol did not induce transcription. (iii) Deletion or mutation of the ERE half-site abolished ligand-induced TPH2 transcription.

Indexed as

Response Elements5' Untranslated RegionsAnimalsCell LineEstradiolEstrogen Receptor betaEstrogensHumansMiceMolecular Sequence DataNitrilesPromoter Regions, GeneticPropionatesRatsSignal TransductionTranscription, Genetic2,3-bis(4-hydroxyphenyl)-propionitrile5' Untranslated RegionsEstradiolEstrogen Receptor betaEstrogensNitrilesPropionatesTPH2 protein, humanTryptophan Hydroxylasediarylpropionitrileestradiolestrogen receptor betaestrogen response elementluciferase reporterserotonin

Identifiers

PMID24033289
PMCPMC5825233
OpenAlexW2053972011

What OpenQuestion holds

Textmetadata
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.