Evidence map›Paper›PMID 27379743›Full record

ArticleThe Journal of clinical endocrinology and metabolism2016

Investigating the KNDy Hypothesis in Humans by Coadministration of Kisspeptin, Neurokinin B, and Naltrexone in Men.

Shakunthala Narayanaswamy, Julia K Prague, Channa N Jayasena, Deborah A Papadopoulou, Maria Mizamtsidi, Amar J Shah, Paul Bassett, Alexander N Comninos, Ali Abbara, Stephen R Bloom and 2 more

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In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
9.7field-weighted citation impact, top 2% 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

14 citing papers in PubMed, 40 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. Article
  5. Review
  6. Hypothalamic Kisspeptin Neurons: Integral Elements of the GnRH System.Reproductive sciences (Thousand Oaks, Calif.) · 2023
    Review
  7. Targeting KNDy neurons to control GnRH pulses.Current opinion in pharmacology · 2022
    Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. 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

12 authors at 3 institutions in 2 countries.

Shakunthala NarayanaswamySection of Investigative Medicine (S.N., J.K.P., C.N.J., D.A.P., M.M., A.J.S., A.N.C., A.A., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom; Statsconsultancy Ltd (P.B.), Amersham, Buckinghamshire HP7 9EN, United Kingdom; and Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905.
Julia K PragueSection of Investigative Medicine (S.N., J.K.P., C.N.J., D.A.P., M.M., A.J.S., A.N.C., A.A., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom; Statsconsultancy Ltd (P.B.), Amersham, Buckinghamshire HP7 9EN, United Kingdom; and Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905.
Channa N JayasenaSection of Investigative Medicine (S.N., J.K.P., C.N.J., D.A.P., M.M., A.J.S., A.N.C., A.A., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom; Statsconsultancy Ltd (P.B.), Amersham, Buckinghamshire HP7 9EN, United Kingdom; and Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905.
Deborah A PapadopoulouSection of Investigative Medicine (S.N., J.K.P., C.N.J., D.A.P., M.M., A.J.S., A.N.C., A.A., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom; Statsconsultancy Ltd (P.B.), Amersham, Buckinghamshire HP7 9EN, United Kingdom; and Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905.
Maria MizamtsidiSection of Investigative Medicine (S.N., J.K.P., C.N.J., D.A.P., M.M., A.J.S., A.N.C., A.A., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom; Statsconsultancy Ltd (P.B.), Amersham, Buckinghamshire HP7 9EN, United Kingdom; and Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905.
Amar J ShahSection of Investigative Medicine (S.N., J.K.P., C.N.J., D.A.P., M.M., A.J.S., A.N.C., A.A., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom; Statsconsultancy Ltd (P.B.), Amersham, Buckinghamshire HP7 9EN, United Kingdom; and Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905.
Paul BassettSection of Investigative Medicine (S.N., J.K.P., C.N.J., D.A.P., M.M., A.J.S., A.N.C., A.A., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom; Statsconsultancy Ltd (P.B.), Amersham, Buckinghamshire HP7 9EN, United Kingdom; and Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905.
Alexander N ComninosSection of Investigative Medicine (S.N., J.K.P., C.N.J., D.A.P., M.M., A.J.S., A.N.C., A.A., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom; Statsconsultancy Ltd (P.B.), Amersham, Buckinghamshire HP7 9EN, United Kingdom; and Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905.
Ali AbbaraSection of Investigative Medicine (S.N., J.K.P., C.N.J., D.A.P., M.M., A.J.S., A.N.C., A.A., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom; Statsconsultancy Ltd (P.B.), Amersham, Buckinghamshire HP7 9EN, United Kingdom; and Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905.
Stephen R BloomSection of Investigative Medicine (S.N., J.K.P., C.N.J., D.A.P., M.M., A.J.S., A.N.C., A.A., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom; Statsconsultancy Ltd (P.B.), Amersham, Buckinghamshire HP7 9EN, United Kingdom; and Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905.
Johannes D VeldhuisSection of Investigative Medicine (S.N., J.K.P., C.N.J., D.A.P., M.M., A.J.S., A.N.C., A.A., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom; Statsconsultancy Ltd (P.B.), Amersham, Buckinghamshire HP7 9EN, United Kingdom; and Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905.
Waljit S DhilloSection of Investigative Medicine (S.N., J.K.P., C.N.J., D.A.P., M.M., A.J.S., A.N.C., A.A., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom; Statsconsultancy Ltd (P.B.), Amersham, Buckinghamshire HP7 9EN, United Kingdom; and Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905.
Imperial College London · GBHammersmith Hospital · GBMayo Clinic · US

Funding

Medical Research Council MR/M024954/1Wellcome Trust
6 · The paper itself

Abstract

contextA subpopulation of hypothalamic neurons colocalize three neuropeptides, namely kisspeptin, neurokinin B (NKB), and dynorphin, collectively termed KNDy neurons. Animal studies suggest they interact to affect pulsatile GnRH release (KNDy hypothesis); kisspeptin stimulates, NKB modulates, and dynorphin (an opioid) inhibits.

objectiveTo investigate the KNDy hypothesis in humans, we assessed for the first time the effects of the coadministration of kisspeptin-54, NKB, and an opioid receptor antagonist, naltrexone, on LH pulsatility (surrogate marker for GnRH pulsatility) and gonadotropin release. DESIGN, SETTING, AND

participantsThis was an ethically approved prospective, single-blinded, placebo-controlled study. Healthy male volunteers (n = 5/group) attended our research facility for eight study visits. INTERVENTION AND

main outcome measureAfter 1 hour of baseline blood sampling, participants received a different intervention at each visit: oral 50 mg naltrexone, 8-hour iv infusions of vehicle, 2.56 nmol/kg · h NKB, 0.1 nmol/kg · h kissspeptin-54 (KP) alone and in combination. Frequent blood sampling to measure plasma gonadotropins and sex steroids was conducted and LH pulsatility was determined using blinded deconvolution analysis.

resultsAll kisspeptin and naltrexone containing groups potently increased LH and LH pulsatility (P < .001 vs vehicle). NKB alone did not affect gonadotropins. NKB+KP had significantly lower increases in gonadotropins compared with kisspeptin alone (P < .01). Naltrexone+KP was the only group to significantly increase LH pulse amplitude (P < .001 vs vehicle).

conclusionsOur results suggest significant interactions between the KNDy neuropeptides on LH pulsatility and gonadotropin release in humans. This has important implications for improving our understanding of GnRH pulse generation in humans.

Indexed as

AdultDrug Therapy, CombinationGene Expression RegulationGonadotropinsHumansKisspeptinsMaleMiddle AgedNaltrexoneNarcotic AntagonistsNeurokinin BNeurotransmitter AgentsProspective StudiesSingle-Blind MethodGonadotropinsKISS1 protein, humanKisspeptinsNaltrexoneNarcotic AntagonistsNeurokinin BNeurotransmitter Agents

Identifiers

PMID27379743
PMCPMC5010567
OpenAlexW2474876498

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.