Evidence map›Paper›PMID 27636018›Full record

Trial reportThe Journal of clinical endocrinology and metabolism2016

Interactions Between Neurokinin B and Kisspeptin in Mediating Estrogen Feedback in Healthy Women.

Karolina Skorupskaite, Jyothis T George, Johannes D Veldhuis, Robert P Millar, Richard A Anderson

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report 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 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
7.5field-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

16 citing papers in PubMed, 48 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 4 institutions in 3 countries.

Karolina SkorupskaiteMRC Centre for Reproductive Health (K.S., J.T.G., R.A.A.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom; Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905; and Mammal Research Unit and Centre for Neuroendocrinology (R.P.M.), University of Pretoria, 0028 Pretoria, South Africa and MRC Receptor Biology Unit, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, 7925 Observatory, South Africa.
Jyothis T GeorgeMRC Centre for Reproductive Health (K.S., J.T.G., R.A.A.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom; Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905; and Mammal Research Unit and Centre for Neuroendocrinology (R.P.M.), University of Pretoria, 0028 Pretoria, South Africa and MRC Receptor Biology Unit, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, 7925 Observatory, South Africa.
Johannes D VeldhuisMRC Centre for Reproductive Health (K.S., J.T.G., R.A.A.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom; Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905; and Mammal Research Unit and Centre for Neuroendocrinology (R.P.M.), University of Pretoria, 0028 Pretoria, South Africa and MRC Receptor Biology Unit, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, 7925 Observatory, South Africa.
Robert P MillarMRC Centre for Reproductive Health (K.S., J.T.G., R.A.A.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom; Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905; and Mammal Research Unit and Centre for Neuroendocrinology (R.P.M.), University of Pretoria, 0028 Pretoria, South Africa and MRC Receptor Biology Unit, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, 7925 Observatory, South Africa.
Richard A AndersonMRC Centre for Reproductive Health (K.S., J.T.G., R.A.A.), The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom; Endocrine Research Unit (J.D.V.), Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905; and Mammal Research Unit and Centre for Neuroendocrinology (R.P.M.), University of Pretoria, 0028 Pretoria, South Africa and MRC Receptor Biology Unit, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, 7925 Observatory, South Africa.
University of Edinburgh · GBMayo Clinic · USMRC Centre for Reproductive Health · GBUniversity of Cape Town · ZA

Funding

Medical Research Council G0701682Wellcome TrustWellcome Trust 102419/Z/13/A
6 · The paper itself

Abstract

contextKisspeptin and neurokinin B (NKB) are obligate for normal gonadotropin secretion, but their hierarchy is unexplored in normal women.

objectiveTo investigate the interaction between kisspeptin and NKB on estrogen-regulated LH secretion.

designWomen were treated with neurokinin-3 receptor (NK3R) antagonist followed by transdermal estradiol to induce LH secretion 48 hours later, with kisspeptin-10 or vehicle infusion during estrogen administration in a 2-way crossover study.

settingClinical research facility. PATIENTS OR OTHER

participantsHealthy females with regular menses. INTERVENTION(S): NK3R antagonist AZD4901 40 mg twice daily orally was taken from cycle day 4-6 for 6 days (n = 10, with 10 no treatment controls). Transdermal estradiol patches (200 μg/d) were applied after 5 days of NK3R antagonist treatment. At 24-hour estradiol treatment, women were randomized to 7-hour kisspeptin-10 (4 μg/kg/h) or vehicle iv infusion, with the alternate infusion in a subsequent cycle. MAIN OUTCOME MEASURE(S): Plasma gonadotropin and estradiol secretion.

resultsAfter an initial suppression, LH secretion was increased 48 hours after estradiol treatment. Kisspeptin-10 increased LH secretion during the inhibitory phase, and LH remained elevated beyond the discontinuation of kisspeptin-10 infusion. NK3R antagonist decreased LH pulse frequency (0.5 ± 0.2 vs 0.7 ± 0.2 pulses/h, P < .05) and stimulated FSH response to kisspeptin-10 infusion (10.7 ± 11.0 vs 5.0 ± 3.6 IU/L, P < .05) with a nonsignificant rise in LH. The duration of LH response was blunted, with LH being lower at 48 hours (7.5 ± 4.8 vs 15.0 ± 11.4 IU/L, P < .05).

conclusionsThese data demonstrate that NKB signaling regulates GnRH/LH secretion in normal women, and is predominantly proximal to kisspeptin in mediating estrogenic positive and negative feedback on LH secretion.

Indexed as

AdolescentAdultCross-Over StudiesEstradiolEstrogensFeedback, PhysiologicalFemaleHumansKisspeptinsLuteinizing HormoneMiddle AgedNeurokinin BNeurotransmitter AgentsReceptors, TachykininSignal TransductionYoung AdultEstradiolEstrogensKISS1 protein, humanKisspeptinsLuteinizing HormoneNeurokinin Bneurokinin receptor 4Neurotransmitter AgentsReceptors, Tachykinin

Identifiers

PMID27636018
PMCPMC5155690
OpenAlexW2520178405

What OpenQuestion holds

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LicenceCC BY
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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.