Evidence map›Paper›PMID 33000549›Full record

ArticleJournal of neuroendocrinology2020

Dopamine-induced interactions of female mouse hypothalamic proteins with progestin receptor-A in the absence of hormone.

Kalpana D Acharya, Sabin A Nettles, Cheryl F Lichti, Katherine Warre-Cornish, Lucia Dutan Polit, Deepak P Srivastava, Larry Denner, Marc J Tetel

Open access · greenAbstract read
In one paragraph

Article in Journal of neuroendocrinology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact, top 88% 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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. 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

8 authors at 4 institutions in 2 countries.

Kalpana D AcharyaNeuroscience Department, Wellesley College, Wellesley, MA, USA.ORCID 0000-0001-6263-4357
Sabin A NettlesNeuroscience Department, Wellesley College, Wellesley, MA, USA.
Cheryl F LichtiDepartment of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
Katherine Warre-CornishDepartment of Basic and Clinical Neuroscience, The Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
Lucia Dutan PolitDepartment of Basic and Clinical Neuroscience, The Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
Deepak P SrivastavaDepartment of Basic and Clinical Neuroscience, The Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0001-6512-9065
Larry DennerDepartment of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
Marc J TetelNeuroscience Department, Wellesley College, Wellesley, MA, USA.ORCID 0000-0002-9843-4071
King's College London · GBWellesley College · USThe University of Texas Medical Branch at Galveston · USWashington University in St. Louis · US

Funding

Coordinating and Bioinformatics Unit for the MMPC/DiaCompU24DK076169 · NIDDK · AUGUSTA UNIVERSITY · PI MCINDOE, RICHARD A. · 2006 to 2018
$42.4M
Mechanisms of Steroid Hormone Action in BrainR01DK061935 · NIDDK · WELLESLEY COLLEGE · PI TETEL, MARC JEFFREY · 2002 to 2014
$2.7M
Medical Research Council MR/L021064/1NIDDK NIH HHS R01 DK061935NIDDK NIH HHS U24 DK076169
6 · The paper itself

Abstract

Neural progestin receptors (PR) function in reproduction, neural development, neuroprotection, learning, memory and the anxiety response. In the absence of progestins, PR can be activated by dopamine (DA) in the rodent hypothalamus to elicit female sexual behaviour. The present study investigated mechanisms of DA activation of PR by testing the hypothesis that proteins from DA-treated hypothalami interact with PR in the absence of progestins. Ovariectomised, oestradiol-primed mice were infused with a D1-receptor agonist, SKF38393 (SKF), into the third ventricle 30 minutes prior to death. Proteins from SKF-treated hypothalami were pulled-down with glutathione S-transferase-tagged mouse PR-A or PR-B and the interactomes were analysed by mass spectrometry. The largest functional group to interact with PR-A in a DA-dependent manner was synaptic proteins. To test the hypothesis that DA activation of PR regulates synaptic proteins, we developed oestradiol-induced PR-expressing hypothalamic-like neurones derived from human-induced pluripotent stem cells (hiPSCs). Similar to progesterone (P4), SKF treatment of hiPSCs increased synapsin1/2 expression. This SKF-dependent effect was blocked by the PR antagonist RU486, suggesting that PR are necessary for this DA-induced increase. The second largest DA-dependent PR-A protein interactome comprised metabolic regulators involved in glucose metabolism, lipid synthesis and mitochondrial energy production. Interestingly, hypothalamic proteins interacted with PR-A, but not PR-B, in an SKF-dependent manner, suggesting that DA promotes the interaction of multiple hypothalamic proteins with PR-A. These in vivo and in vitro results indicate novel mechanisms by which DA can differentially activate PR isoforms in the absence of P4 and provide a better understanding of ligand-independent PR activation in reproductive, metabolic and mental health disorders in women.

Indexed as

AnimalsDopamineFemaleHypothalamusMiceMice, Inbred C57BLNerve Tissue ProteinsNeuronsProgesteroneProtein BindingProtein IsoformsReceptors, ProgesteroneSignal TransductionDopamineNerve Tissue ProteinsProgesteroneProtein IsoformsReceptors, Progesteroneenergy homeostasisinduced pluripotent stem cellsmetabolismprogesteronesynapse

Identifiers

PMID33000549
PMCPMC7591852
OpenAlexW3081622151

What OpenQuestion holds

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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.