Evidence map›Paper›PMID 25011649›Full record

ArticleNeuroendocrinology2014

Endogenous kisspeptin tone is a critical excitatory component of spontaneous GnRH activity and the GnRH response to NPY and CART.

Saurabh Verma, Melissa A Kirigiti, Robert P Millar, Kevin L Grove, M Susan Smith

Open access · bronzeAbstract read
In one paragraph

Article in Neuroendocrinology, 2014. 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
3.6field-weighted citation impact, top 8% 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, 19 citations in OpenAlex.

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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

5 authors at 3 institutions in 4 countries.

Saurabh VermaDivision of Diabetes, Obesity, & Metabolism, Oregon National Primate Research Center, Oregon Health & Sciences University, Beaverton, Oreg., USA.
Melissa A Kirigiti
Robert P Millar
Kevin L Grove
M Susan Smith
Iowa State University · USOregon National Primate Research Center · USDiabetes Australia · AU

Funding

Upgrade of confocal microscopy at the Oregon National Primate Research CenterP51OD011092 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Bonnie J. Nagel · 2012 to 2026
$203.9M
YR 50 PROJ- ROBERTS PRIMATE ISLETP51RR000163 · NCRR · OREGON REGIONAL PRIMATE RESEARCH CENTER · PI PICKER, LOUIS J. · 1985 to 2011
$140.8M
CONTROL OF GONADOTROPIN SECRETION DURING LACTATIONR01HD014643 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GROVE, KEVIN L · 1985 to 2015
$4.0M
NCRR NIH HHS P51 RR000163NICHD NIH HHS HD014643NICHD NIH HHS R01 HD014643NIH HHS OD011092NIH HHS P51 OD011092
6 · The paper itself

Abstract

BACKGROUND/

aimsKisspeptin is the major excitatory regulator of gonadotropin-releasing hormone (GnRH) neurons and is responsible for basal GnRH/LH release and the GnRH/LH surge. Although it is widely assumed, based on mutations in kisspeptin and Kiss1R, that kisspeptin acts to sustain basal GnRH neuronal activity, there have been no studies to investigate whether endogenous basal kisspeptin tone plays a direct role in basal spontaneous GnRH neuronal excitability. It is also of interest to examine possible interactions between endogenous kisspeptin tone and other neuropeptides that have direct effects on GnRH neurons, such as neuropeptide Y (NPY) or cocaine- and amphetamine-regulated transcript (CART), since the activity of all these neuropeptides changes during states of negative energy balance.

methodsLoose cell-attached and whole-cell current patch-clamp recordings were made from GnRH-GFP neurons in hypothalamic slices from female and male rats.

resultsKisspeptin activated GnRH neurons in a concentration-dependent manner with an EC50 of 3.32 ± 0.02 nM. Surprisingly, a kisspeptin antagonist, Peptide 347, suppressed spontaneous activity in GnRH neurons, demonstrating the essential nature of the endogenous kisspeptin tone. Furthermore, inhibition of endogenous kisspeptin tone blocked the direct activation of GnRH cells that occurs in response to antagonism of NPY Y5 receptor or by CART.

conclusionsOur electrophysiology studies suggest that basal endogenous kisspeptin tone is not only essential for spontaneous GnRH neuronal firing, but it is also required for the net excitatory effects of other neuropeptides, such as CART or NPY antagonism, on GnRH neurons. Therefore, endogenous kisspeptin tone could serve as the linchpin in GnRH activation or inhibition.

Indexed as

Action PotentialsAnimalsCocaine- and Amphetamine-Regulated Transcript ProteinEstradiolFemaleGonadotropin-Releasing HormoneGreen Fluorescent ProteinsIn Vitro TechniquesKisspeptinsMaleNerve Tissue ProteinsNeuronsNeuropeptide YOvariectomyPatch-Clamp TechniquesPreoptic AreaCocaine- and Amphetamine-Regulated Transcript Proteinenhanced green fluorescent proteinEstradiolGonadotropin-Releasing HormoneGreen Fluorescent ProteinsKiss1 protein, ratKisspeptinsNerve Tissue ProteinsNeuropeptide YSodium Channel BlockersTetrodotoxin

Identifiers

PMID25011649
PMCPMC4201869
OpenAlexW2069084149

What OpenQuestion holds

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Registered trials

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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.