Evidence map›Paper›PMID 27871072›Full record

ArticleNeuroendocrinology2017

Testosterone Rapidly Augments Retrograde Endocannabinoid Signaling in Proopiomelanocortin Neurons to Suppress Glutamatergic Input from Steroidogenic Factor 1 Neurons via Upregulation of Diacylglycerol Lipase-α.

Kristie Conde, Carolina Fabelo, William C Krause, Robert Propst, Jordan Goethel, Daniel Fischer, Jin Hur, Cecilia Meza, Holly A Ingraham, Edward J Wagner

Open access · bronzeAbstract read
In one paragraph

Article in Neuroendocrinology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 13% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

  1. Pooled it
  2. Dietary Manganese Modulates Microbiota and Intestinal N-Acylethanolamines in a Sex-Specific Manner in Mice With Diet-Induced Obesity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  3. Article
  4. Endocannabinoid System and Metabolism: The Influences of Sex.International journal of molecular sciences · 2024
    Review
  5. Parvalbumin interneuron mGluNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Article
  6. Review
  7. Parvalbumin interneuron mGlubioRxiv : the preprint server for biology · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. The Roles of Androgens in Humans: Biology, Metabolic Regulation and Health.International journal of molecular sciences · 2022
    Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Birdsong as a window into language origins and evolutionary neuroscience.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020
    Review
  19. Article
  20. 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

10 authors at 2 institutions in 1 country.

Kristie CondeDepartment of Basic Medical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA, USA.
Carolina Fabelo
William C Krause
Robert Propst
Jordan Goethel
Daniel Fischer
Jin Hur
Cecilia Meza
Holly A Ingraham
Edward J Wagner
Western University of Health Sciences · USUniversity of California, San Francisco · US

Funding

UCSF Nutrition Obesity Research CenterP30DK098722 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHRISTIAN VAISSE · 2015 to 2026
$14.6M
Orphan Nuclear Receptors in Development and PhysiologyR01DK063592 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI INGRAHAM, HOLLY A. · 2003 to 2013
$3.5M
Mapping Hypothalamic Neurocircuits Controlling Physical ActivityR01DK099722 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI INGRAHAM, HOLLY A. · 2014 to 2018
$2.0M
Sex Differences in the Cannabioid Regulation of Energy HomeostasisR15DA024314 · NIDA · WESTERN UNIVERSITY OF HEALTH SCIENCES · PI WAGNER, EDWARD J · 2008 to 2020
$1.5M
Opioid mediation of progesterone actions in a reproductive behavior circuitR01HD058638 · NICHD · CALIFORNIA STATE UNIVERSITY LONG BEACH · PI SINCHAK, KEVIN · 2009 to 2013
$1.4M
NICHD NIH HHS R01 HD058638NIDA NIH HHS R15 DA024314NIDDK NIH HHS P30 DK098722NIDDK NIH HHS R01 DK063592NIDDK NIH HHS R01 DK099722
6 · The paper itself

Abstract

Testosterone exerts profound effects on reproduction and energy homeostasis. Like other orexigenic hormones, it increases endocannabinoid tone within the hypothalamic feeding circuitry. Therefore, we tested the hypothesis that testosterone upregulates the expression of diacylglycerol lipase (DAGL)α in the hypothalamic arcuate nucleus (ARC) to increase energy intake via enhanced endocannabinoid-mediated retrograde inhibition of anorexigenic proopiomelanocortin (POMC) neurons. Energy intake, meal patterns, and energy expenditure were evaluated in orchidectomized, male guinea pigs treated subcutaneously with testosterone propionate (TP; 400 μg) or its sesame oil vehicle (0.1 mL). TP rapidly increased energy intake, meal size, O2 consumption, CO2 production, and metabolic heat production, all of which were antagonized by prior administration of the DAGL inhibitor orlistat (3 μg) into the third ventricle. These orlistat-sensitive, TP-induced increases in energy intake and expenditure were temporally associated with a significant elevation in ARC DAGLα expression. Electrophysiological recordings in hypothalamic slices revealed that TP potentiated depolarization-induced suppression of excitatory glutamatergic input onto identified ARC POMC neurons, which was also abolished by orlistat (3 μM), the CB1 receptor antagonist AM251 (1 μM), and the AMP-activated protein kinase inhibitor compound C (30 μM) and simulated by transient bath application of the dihydrotestosterone mimetic Cl-4AS-1 (100 nM) and testosterone-conjugated bovine serum albumin (100 nM). Thus, testosterone boosts DAGLα expression to augment retrograde, presynaptic inhibition of glutamate release onto ARC POMC neurons that, in turn, increases energy intake and expenditure. These studies advance our understanding of how androgens work within the hypothalamic feeding circuitry to affect changes in energy balance.

Indexed as

Action PotentialsAnimalsCerebral CortexEndocannabinoidsEnergy IntakeEnzyme InhibitorsEstradiolExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsFemaleGABA AntagonistsGlutamic AcidGuinea PigsLactonesLipoprotein LipaseMaleEndocannabinoidsEnzyme InhibitorsEstradiolestradiol 3-benzoateExcitatory Amino Acid AntagonistsGABA AntagonistsgabazineGlutamic AcidLactonesLipoprotein LipaseOrlistatPro-OpiomelanocortinPyridazinesSteroidogenic Factor 1Testosterone2-ArachidonoylglycerolDepolarization-induced suppression of excitationDiacylglycerol lipase-αEstradiolProopiomelanocortinTestosterone

Identifiers

PMID27871072
PMCPMC5839320
OpenAlexW2557052814

What OpenQuestion holds

Textmetadata
LicenceTDM
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.