Evidence map›Paper›PMID 22851703›Full record

ArticleMolecular endocrinology (Baltimore, Md.)2012

Stress levels of glucocorticoids inhibit LHβ-subunit gene expression in gonadotrope cells.

Kellie M Breen, Varykina G Thackray, Tracy Hsu, Rachel A Mak-McCully, Djurdjica Coss, Pamela L Mellon

Open access · bronzeAbstract read
In one paragraph

Article in Molecular endocrinology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

29 citing papers in PubMed, 56 citations in OpenAlex.

  1. Trial
  2. Omega-3 Fatty Acid Supplementation Lowers Serum FSH in Normal Weight But Not Obese Women.The Journal of clinical endocrinology and metabolism · 2016
    Trial
  3. Trial
  4. Review
  5. Review
  6. Stress and parental behaviors.Neuroscience research · 2025
    Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Unexpected Role of Physiological Estrogen in Acute Stress-Induced Memory Deficits.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  17. Review
  18. Article
  19. Article
  20. Review
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 1 institution in 1 country.

Kellie M BreenDepartment of Reproductive Medicine/Neuroscience, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0674, USA.
Varykina G Thackray
Tracy Hsu
Rachel A Mak-McCully
Djurdjica Coss
Pamela L Mellon
University of California, San Diego · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
Yeast Genetics and Stress Response Genes-BiomedicalP42ES010337 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2000 to 2022
$69.8M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
The Interaction of Neuroendocrine Repro. Function and Metabolic SignalingU54HD012303 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI OLEFSKY, JERROLD MICHAEL · 1999 to 2013
$18.0M
PROJECT 3 - Steroid-Metabolic Interactions In the Control of GnRH NeuronsU54HD028934 · NICHD · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI MARSHALL, JOHN C · 1998 to 2013
$16.5M
Neurosciences Graduate Training ProgramT32NS061847 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Brenda L Bloodgood · 2008 to 2026
$7.7M
The Role of FSH in Female InfertilityP50HD012303 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MELLON, PAMELA L · 1985 to 2020
$7.5M
TRAINING IN REPRODUCTIVE SCIENCEST32HD007203 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PAMELA L MELLON · 1988 to 2026
$4.8M
NEUROSECRETORY GENE EXPRESSION IN THE HYPOTHALAMUSR01DK044838 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MELLON, PAMELA L · 1991 to 2011
$3.8M
Neurosecretory Gene Expression in the HypothalamusR01HD072754 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MELLON, PAMELA L · 2012 to 2016
$1.7M
Transcriptional control of pituitary gonadotropin genesR01HD067448 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI THACKRAY, VARYKINA G · 2011 to 2015
$1.6M
The Role of AP-1 in the GonadotropeR01HD057549 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI COSS, DJURDJICA · 2009 to 2013
$1.6M
NCI NIH HHS P30 CA023100NICHD NIH HHS K99 HD060947NICHD NIH HHS L50 HD056572NICHD NIH HHS P50 HD012303NICHD NIH HHS R00 HD060947NICHD NIH HHS R01 HD020377NICHD NIH HHS R01 HD057549NICHD NIH HHS R01 HD067448NICHD NIH HHS R01 HD072754NICHD NIH HHS R03 HD054595NICHD NIH HHS R21 HD058752NICHD NIH HHS T32 HD007203NICHD NIH HHS U54 HD012303NICHD NIH HHS U54 HD028934NIDDK NIH HHS K01 DK080467NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK044838NIDDK NIH HHS R01DK044838NIEHS NIH HHS P42 ES010337NINDS NIH HHS T32 NS061847
6 · The paper itself

Abstract

Increased glucocorticoid secretion is a common response to stress and has been implicated as a mediator of reproductive suppression upon the pituitary gland. We utilized complementary in vitro and in vivo approaches in the mouse to investigate the role of glucocorticoids as a stress-induced intermediate capable of gonadotrope suppression. Repeated daily restraint stress lengthened the ovulatory cycle of female mice and acutely reduced GnRH-induced LH secretion and synthesis of LH β-subunit (LHβ) mRNA, coincident with increased circulating glucocorticoids. Administration of a stress level of glucocorticoid, in the absence of stress, blunted LH secretion in ovariectomized female mice, demonstrating direct impairment of reproductive function by glucocorticoids. Supporting a pituitary action, glucocorticoid receptor (GR) is expressed in mouse gonadotropes and treatment with glucocorticoids reduces GnRH-induced LHβ expression in immortalized mouse gonadotrope cells. Analyses revealed that glucocorticoid repression localizes to a region of the LHβ proximal promoter, which contains early growth response factor 1 (Egr1) and steroidogenic factor 1 sites critical for GnRH induction. GR is recruited to this promoter region in the presence of GnRH, but not by dexamethasone alone, confirming the necessity of the GnRH response for GR repression. In lieu of GnRH, Egr1 induction is sufficient for glucocorticoid repression of LHβ expression, which occurs via GR acting in a DNA- and dimerization-independent manner. Collectively, these results expose the gonadotrope as an important neuroendocrine site impaired during stress, by revealing a molecular mechanism involving Egr1 as a critical integrator of complex formation on the LHβ promoter during GnRH induction and GR repression.

Indexed as

Gene ExpressionAnimalsCell LineDown-RegulationEstrous CycleFemaleGlucocorticoidsGonadotrophsGonadotropin-Releasing HormoneLuteinizing Hormone, beta SubunitMiceMice, Inbred C57BLPromoter Regions, GeneticRatsReceptors, GlucocorticoidResponse ElementsGlucocorticoidsGonadotropin-Releasing HormoneLuteinizing Hormone, beta SubunitReceptors, Glucocorticoid

Identifiers

PMID22851703
PMCPMC3458227
OpenAlexW2021052928

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.