Evidence map›Paper›PMID 24424047›Full record

ArticleEndocrinology2014

Impaired GABAB receptor signaling dramatically up-regulates Kiss1 expression selectively in nonhypothalamic brain regions of adult but not prepubertal mice.

Noelia P Di Giorgio, Sheila J Semaan, Joshua Kim, Paula V López, Bernhard Bettler, Carlos Libertun, Victoria A Lux-Lantos, Alexander S Kauffman

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
7.6field-weighted citation impact, top 3% 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

38 citing papers in PubMed, 56 citations in OpenAlex.

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  10. Estrogen-Regulated Lateral Septal Kisspeptin Neurons Abundantly Project to GnRH Neurons and the Hypothalamic Supramammillary Nucleus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
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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

8 authors at 5 institutions in 3 countries.

Noelia P Di GiorgioInstitute of Biology and Experimental Medicine-CONICET (N.P.D.G., P.V.L., C.L., V.A.L-L.), Buenos Aires, Argentina; Department of Reproductive Medicine (S.J.S., J.K., A.S.K.), University of California San Diego, La Jolla, California; Department of Biomedicine (B.B.), University of Basel, Basel, Switzerland; and Department of Physiology (C.L.), University of Buenos Aires, Buenos Aires, Argentina.
Sheila J Semaan
Joshua Kim
Paula V López
Bernhard Bettler
Carlos Libertun
Victoria A Lux-Lantos
Alexander S Kauffman
University of California, San Diego · USConsejo Nacional de Investigaciones Científicas y Técnicas · ARExperimental Medicine and Biology Institute · ARUniversity of Basel · CHUniversity of Buenos Aires · AR

Funding

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 MELLON, PAMELA L · 1999 to 2013
$18.0M
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
NICHD NIH HHS P50 HD012303NICHD NIH HHS T32 HD007203NICHD NIH HHS U54 HD012303NIDDK NIH HHS P30 DK063491
6 · The paper itself

Abstract

Kisspeptin, encoded by Kiss1, stimulates reproduction and is synthesized in the hypothalamic anteroventral periventricular and arcuate nuclei. Kiss1 is also expressed at lower levels in the medial amygdala (MeA) and bed nucleus of the stria terminalis (BNST), but the regulation and function of Kiss1 there is poorly understood. γ-Aminobutyric acid (GABA) also regulates reproduction, and female GABAB1 receptor knockout (KO) mice have compromised fertility. However, the interaction between GABAB receptors and Kiss1 neurons is unknown. Here, using double-label in situ hybridization, we first demonstrated that a majority of hypothalamic Kiss1 neurons coexpress GABAB1 subunit, a finding also confirmed for most MeA Kiss1 neurons. Yet, despite known reproductive impairments in GABAB1KO mice, Kiss1 expression in the anteroventral periventricular and arcuate nuclei, assessed by both in situ hybridization and real-time PCR, was identical between adult wild-type and GABAB1KO mice. Surprisingly, however, Kiss1 levels in the BNST and MeA, as well as the lateral septum (a region normally lacking Kiss1 expression), were dramatically increased in both GABAB1KO males and females. The increased Kiss1 levels in extrahypothalamic regions were not caused by elevated sex steroids (which can increase Kiss1 expression), because circulating estradiol and testosterone were equivalent between genotypes. Interestingly, increased Kiss1 expression was not detected in the MeA or BNST in prepubertal KO mice of either sex, indicating that the enhancements in extrahypothalamic Kiss1 levels initiate during/after puberty. These findings suggest that GABAB signaling may normally directly or indirectly inhibit Kiss1 expression, particularly in the BNST and MeA, and highlight the importance of studying kisspeptin populations outside the hypothalamus.

Indexed as

Gene Expression RegulationSignal TransductionAmygdalaAnimalsArcuate Nucleus of HypothalamusBrain MappingEstradiolFemalegamma-Aminobutyric AcidGenotypeHypothalamusImmunohistochemistryKisspeptinsMaleMiceMice, KnockoutEstradiolgamma-Aminobutyric AcidKiss1 protein, mouseKisspeptinsReceptors, GABA-BTestosterone

Identifiers

PMID24424047
PMCPMC3929734
OpenAlexW2042226434

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.