Evidence map›Paper›PMID 31754709›Full record

ArticleEndocrinology2020

Sex-Dependent Mechanisms of Glucocorticoid Regulation of the Mouse Hypothalamic Corticotropin-Releasing Hormone Gene.

Ashley L Heck, Maranda K Thompson, Rosalie M Uht, Robert J Handa

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.0field-weighted citation impact, top 29% 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

15 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Sex-specific and developmental effects of early life adversity on stress reactivity are rescued by postnatal knockdown of 5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. 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

4 authors at 3 institutions in 1 country.

Ashley L HeckDepartment of Biomedical Sciences, Colorado State University, Fort Collins, Colorado.
Maranda K ThompsonDepartment of Basic Medical Sciences, University of Arizona, Phoenix, Arizona.
Rosalie M UhtDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas.
Robert J HandaDepartment of Biomedical Sciences, Colorado State University, Fort Collins, Colorado.
Colorado State University · USUniversity of Arizona · USUniversity of North Texas · US

Funding

Estrogen Regulation of the Hypothalamo-Pituitary-Adrenal AxisR01DK105826 · NIDDK · COLORADO STATE UNIVERSITY · PI MYERS, BRENT PHILIP · 2015 to 2020
$2.1M
GR-Mediated Epigenetic Regulation of the CRH GeneR01MH082900 · NIMH · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI UHT, ROSALIE MARIE · 2009 to 2013
$1.8M
NIDDK NIH HHS R01 DK105826NIMH NIH HHS R01 MH082900
6 · The paper itself

Abstract

To limit excessive glucocorticoid secretion following hypothalamic-pituitary-adrenal (HPA) axis stimulation, circulating glucocorticoids inhibit corticotropin-releasing hormone (CRH) expression in paraventricular nucleus (PVN) neurons. As HPA function differs between sexes and depends on circulating estradiol (E2) levels in females, we investigated sex/estrous stage-dependent glucocorticoid regulation of PVN Crh. Using NanoString nCounter technology, we first demonstrated that adrenalectomized (ADX'd) diestrous female (low E2), but not male or proestrous female (high E2), mice exhibited a robust decrease in PVN CRH mRNA following 2-day treatment with the glucocorticoid receptor (GR) agonist RU28362. Immunohistochemical analysis of PVN CRH neurons in Crh-IRES-Cre;Ai14 mice, where TdTomato fluorescence permanently tags CRH-expressing neurons, showed similarly abundant co-expression of GR-immunoreactivity in males, diestrous females, and proestrous females. However, we identified sex/estrous stage-related glucocorticoid regulation or expression of GR transcriptional coregulators. Out of 17 coregulator genes examined using nCounter multiplex analysis, mRNAs that were decreased by RU28362 in ADX'd mice in a sex/estrous stage-dependent fashion included: GR (males = diestrous females > proestrous females), signal transducer and activator of transcription 3 (STAT3) (males < diestrous = proestrous), and HDAC1 (males < diestrous > proestrous). Steroid receptor coactivator 3 (SRC-3), nuclear corepressor 1 (NCoR1), heterogeneous nuclear ribonucleoprotein U (hnrnpu), CREB binding protein (CBP) and CREB-regulated transcription coactivator 2 (CRTC2) mRNAs were lower in ADX'd diestrous and proestrous females versus males. Additionally, most PVN CRH neurons co-expressed methylated CpG binding protein 2 (MeCP2)-immunoreactivity in diestrous female and male Crh-IRES-Cre;Ai14 mice. Our findings collectively suggest that GR's sex-dependent regulation of PVN Crh may depend upon differences in the GR transcriptional machinery and an underlying influence of E2 levels in females.

Indexed as

AdrenalectomyAndrostanolsAnimalsCorticotropin-Releasing HormoneEstradiolEstrous CycleFemaleGene Expression RegulationGlucocorticoidsGonadotropin-Releasing HormoneHypothalamusMaleMiceMice, Inbred StrainsNeuronsRNA, Messenger11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-oneAndrostanolsCorticotropin-Releasing HormoneEstradiolGlucocorticoidsGonadotropin-Releasing HormoneRNA, Messengeradrenalectomycorticotropin-releasing hormone (CRH)glucocorticoid receptor (GR)paraventricular nucleus (PVN)sex differences

Identifiers

PMID31754709
PMCPMC7188085
OpenAlexW2990560546

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.