Evidence map›Paper›PMID 25981521›Full record

ArticleReproductive biology and endocrinology : RB&E2015

Activity of the porcine gonadotropin-releasing hormone receptor gene promoter is partially conferred by a distal gonadotrope specific element (GSE) within an upstream enhancing region, two proximal GSEs and a retinoid X receptor binding site.

Rebecca A Cederberg, Jacqueline E Smith, Emily A McDonald, Chanho Lee, Amy R Perkins, Brett R White

Open access · goldAbstract read
In one paragraph

Article in Reproductive biology and endocrinology : RB&E, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Frontiers in endocrinology · 2025
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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

6 authors at 2 institutions in 1 country.

Rebecca A CederbergLaboratory of Reproductive Biology, Department of Animal Science, Institute of Agriculture and Natural Resources, University of Nebraska-Lincoln, Lincoln, Nebraska, USA. rcederberg2@unl.edu.
Jacqueline E SmithLaboratory of Reproductive Biology, Department of Animal Science, Institute of Agriculture and Natural Resources, University of Nebraska-Lincoln, Lincoln, Nebraska, USA. jsm@stowers.org.
Emily A McDonaldLaboratory of Reproductive Biology, Department of Animal Science, Institute of Agriculture and Natural Resources, University of Nebraska-Lincoln, Lincoln, Nebraska, USA. emcdonald1@lifespan.org.
Chanho LeeLaboratory of Reproductive Biology, Department of Animal Science, Institute of Agriculture and Natural Resources, University of Nebraska-Lincoln, Lincoln, Nebraska, USA. chanho.lee@huskers.unl.edu.
Amy R PerkinsLaboratory of Reproductive Biology, Department of Animal Science, Institute of Agriculture and Natural Resources, University of Nebraska-Lincoln, Lincoln, Nebraska, USA. acropp@hotmail.com.
Brett R WhiteLaboratory of Reproductive Biology, Department of Animal Science, Institute of Agriculture and Natural Resources, University of Nebraska-Lincoln, Lincoln, Nebraska, USA. bwhite2@unl.edu.
University of Nebraska–Lincoln · USRhode Island Hospital · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRegulation of gonadotropin-releasing hormone (GnRH) receptor (GnRHR) numbers on gonadotropes within the anterior pituitary gland represents a critical point for control of reproductive function. Binding of GnRH to its receptor regulates follicle stimulating hormone (FSH) and luteinizing hormone (LH) release and levels of this G-protein coupled receptor on the surface of gonadotropes determines their sensitivity to GnRH pulses. While transcriptional regulation of this gene has been studied in mice, rats, humans and sheep, little is known about its regulation in the pig, an important agricultural species and human research model.

methodsWe isolated 5118 bp of 5' flanking sequence for the porcine GnRHR gene and generated luciferase reporter vectors. Deletion and mutation constructs were evaluated in gonadotrope-derived alphaT3-1 cells to determine regions important for gene transcription. Additionally, electrophoretic mobility shift assays (EMSAs) were performed to identify transcription factors binding to the GnRHR promoter.

resultsTransient transfections revealed that the GnRHR promoter was functional in alphaT3-1 cells but not in cells of non-gonadotrope origin. Mutation of the highly conserved gonadotrope specific element (GSE) located at -179/-171 of proximal promoter completely ablated luciferase activity, whereas mutation of another GSE at -315/-310 reduced activity by 34%. Consistent with this, EMSAs using alphaT3-1 nuclear extracts and a steroidogenic factor (SF)1 antibody confirmed SF1 binding to both GSEs. EMSAs also demonstrated that a retinoid X receptor (RXR) binding site at -279/-274 binds RXRalpha and RXRbeta and mutation of this site eliminated promoter activity. Transient transfection of alphaT3-1 cells with reporter vectors containing selective removal of 5' flanking region for the porcine GnRHR gene indicated that the -1915/-1431 segment was important for promoter activity. Definition of this region via transfection assays and EMSAs revealed an upstream enhancing region located at -1779/-1667 that increases porcine GnRHR gene expression in alphaT3-1 cells and includes a SF1 binding site at -1760/-1753.

conclusionsPorcine GnRHR promoter activity in alphaT3-1 cells is partially conferred by a distal GSE, two proximal GSEs and a RXR binding site. Basal gonadotrope expression of the porcine GnRHR gene uniquely involves three GSEs and RXR is newly identified as a regulator of GnRHR promoter activity.

Indexed as

Gene Expression RegulationPromoter Regions, GeneticAnimalsBinding SitesGonadotropin-Releasing HormoneResponse ElementsRetinoid X ReceptorsSwineGonadotropin-Releasing HormoneRetinoid X Receptors

Identifiers

PMID25981521
PMCPMC4461931
OpenAlexW2099546847

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.