Evidence map›Paper›PMID 39248143›Full record

ArticleEndocrinology2024

ZEB1 Inhibits LHβ Subunit Transcription When Overexpressed, but Is Dispensable for LH Synthesis in Mice.

Hailey Schultz, Xiang Zhou, Carlos Agustín Isidro Alonso, Luisina Ongaro, Yeu-Farn Lin, Mary Loka, Thomas Brabletz, Simone Brabletz, Marc P Stemmler, Ulrich Boehm and 1 more

Abstract read
In one paragraph

Article in Endocrinology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. 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

11 authors.

Hailey SchultzDepartment of Anatomy and Cell Biology, McGill University, Montréal, Québec H3G 1Y6, Canada.
Xiang ZhouDepartment of Pharmacology and Therapeutics, McGill University, Montréal, Québec H3G 1Y6, Canada.
Carlos Agustín Isidro AlonsoDepartment of Pharmacology and Therapeutics, McGill University, Montréal, Québec H3G 1Y6, Canada.
Luisina OngaroDepartment of Pharmacology and Therapeutics, McGill University, Montréal, Québec H3G 1Y6, Canada.ORCID 0000-0002-5449-2894
Yeu-Farn LinDepartment of Pharmacology and Therapeutics, McGill University, Montréal, Québec H3G 1Y6, Canada.
Mary LokaIntegrated Program in Neuroscience, McGill University, Montréal, Québec H3G 1Y6, Canada.
Thomas BrabletzDepartment of Experimental Medicine 1, Nikolaus-Fiebiger Center for Molecular Medicine, FAU University Erlangen-Nürnberg, Erlangen 91054, Germany.
Simone BrabletzDepartment of Experimental Medicine 1, Nikolaus-Fiebiger Center for Molecular Medicine, FAU University Erlangen-Nürnberg, Erlangen 91054, Germany.
Marc P StemmlerDepartment of Experimental Medicine 1, Nikolaus-Fiebiger Center for Molecular Medicine, FAU University Erlangen-Nürnberg, Erlangen 91054, Germany.
Ulrich BoehmDepartment of Experimental Pharmacology, Center for Molecular Signaling, Saarland University School of Medicine, Homburg 66421, Germany.
Daniel J BernardDepartment of Anatomy and Cell Biology, McGill University, Montréal, Québec H3G 1Y6, Canada.ORCID 0000-0001-5365-5586

Funding

CIHR PJT-169184Doctoral Graduate ScholarshipsFonds de recherche du Québec - Nature et technologiesNational Sciences and Engineering Research Council of Canada
6 · The paper itself

Abstract

Luteinizing hormone (LH), a heterodimeric glycoprotein produced by pituitary gonadotrope cells, regulates gonadal function. Hypothalamic gonadotropin-releasing hormone (GnRH) stimulates LH synthesis and secretion. GnRH induces LHβ subunit (Lhb) expression via the transcription factor, early growth response 1 (EGR1), acting on the Lhb promoter. In contrast, overexpression of zinc finger E-box binding homeobox 1 (ZEB1) represses LH production in mice, but the underlying mechanism was not previously elucidated. Here, we observed that ZEB1 inhibited GnRH-stimulated but not basal Lhb mRNA expression in homologous murine LβT2 cells. Moreover, ZEB1 blocked GnRH and/or EGR1 induction of murine Lhb but not human LHB promoter-reporter activity in these cells. Using chimeric reporters, we mapped the species-specific ZEB1 sensitivity to sequence differences, including in Z- and E-boxes, in the proximal Lhb/LHB promoters, immediately upstream of the transcription start sites. ZEB1 bound to the murine Lhb promoter with higher affinity than to the human LHB promoter in this region. To examine ZEB1's physiological role in LH synthesis, we characterized gonadotrope-specific Zeb1 knockout mice. Loss of ZEB1 in gonadotropes did not affect LH production or secretion. Collectively, the data suggest that ZEB1, when overexpressed, can inhibit GnRH/EGR1 induction of murine Lhb transcription but does not play a necessary role in LH synthesis in mice.

Indexed as

Gonadotropin-Releasing HormoneLuteinizing HormoneLuteinizing Hormone, beta SubunitPromoter Regions, GeneticZinc Finger E-box-Binding Homeobox 1AnimalsCell LineEarly Growth Response Protein 1Gene Expression RegulationHumansMaleMiceMice, KnockoutTranscription, GeneticEarly Growth Response Protein 1Egr1 protein, mouseGonadotropin-Releasing HormoneLuteinizing HormoneLuteinizing Hormone, beta SubunitZEB1 protein, mouseZinc Finger E-box-Binding Homeobox 1gonadotropeknockoutpituitarytranscriptionZEB1

Identifiers

PMID39248143
PMCPMC11422717

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.