Evidence map›Paper›PMID 26937713›Full record

ArticleEndocrinology2016

Ablation of KNDy Neurons Results in Hypogonadotropic Hypogonadism and Amplifies the Steroid-Induced LH Surge in Female Rats.

Melinda A Mittelman-Smith, Sally J Krajewski-Hall, Nathaniel T McMullen, Naomi E Rance

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
12.3field-weighted citation impact, top 1% 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

31 citing papers in PubMed, 73 citations in OpenAlex.

  1. Article
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  15. In vivo imaging of the GnRH pulse generator reveals a temporal order of neuronal activation and synchronization during each pulse.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  16. Optogenetic stimulation of Kiss1Frontiers in endocrinology · 2022
    Article
  17. Review
  18. Review
  19. Frontiers in endocrinology · 2021
    Article
  20. Makorin rings the kisspeptin bell to signal pubertal initiation.The Journal of clinical investigation · 2020
    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

4 authors at 1 institution in 1 country.

Melinda A Mittelman-SmithDepartments of Pathology (M.A.M.-S., S.J.K.-H., N.E.R.) and Cellular and Molecular Medicine and Neurology (N.T.M., N.E.R.) and The Evelyn F. McKnight Brain Institute (N.E.R.), University of Arizona College of Medicine, Tucson, Arizona 85724.
Sally J Krajewski-HallDepartments of Pathology (M.A.M.-S., S.J.K.-H., N.E.R.) and Cellular and Molecular Medicine and Neurology (N.T.M., N.E.R.) and The Evelyn F. McKnight Brain Institute (N.E.R.), University of Arizona College of Medicine, Tucson, Arizona 85724.
Nathaniel T McMullenDepartments of Pathology (M.A.M.-S., S.J.K.-H., N.E.R.) and Cellular and Molecular Medicine and Neurology (N.T.M., N.E.R.) and The Evelyn F. McKnight Brain Institute (N.E.R.), University of Arizona College of Medicine, Tucson, Arizona 85724.
Naomi E RanceDepartments of Pathology (M.A.M.-S., S.J.K.-H., N.E.R.) and Cellular and Molecular Medicine and Neurology (N.T.M., N.E.R.) and The Evelyn F. McKnight Brain Institute (N.E.R.), University of Arizona College of Medicine, Tucson, Arizona 85724.
University of Arizona · US

Funding

PROJECT 3 - Steroid-Metabolic Interactions In the Control of GnRH NeuronsU54HD028934 · NICHD · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI MOENTER, SUZANNE M · 1998 to 2013
$16.5M
Role of preoptic NK3R neurons in the estrogen modulation of body temperatureR01AG047887 · NIA · UNIVERSITY OF ARIZONA · PI RANCE, NAOMI E · 2014 to 2018
$1.5M
The role of neurokinin B in the generation of menopausal flushesR01AG032315 · NIA · UNIVERSITY OF ARIZONA · PI RANCE, NAOMI E · 2008 to 2012
$1.4M
NIA NIH HHS R01 AG032315NIA NIH HHS R01 AG047887NICHD NIH HHS U54 HD028934
6 · The paper itself

Abstract

In the human infundibular (arcuate) nucleus, a subpopulation of neurons coexpress kisspeptin and neurokinin B (NKB), 2 peptides required for normal reproductive function. A homologous group of neurons exists in the arcuate nucleus of rodents, termed KNDy neurons based on the coexpression of kisspeptin, NKB, and dynorphin. To study their function, we recently developed a method to selectively ablate KNDy neurons using NK3-SAP, a neurokinin 3 receptor agonist conjugated to saporin (SAP). Here, we ablated KNDy neurons in female rats to determine whether these neurons are required for estrous cyclicity and the steroid induced LH surge. NK3-SAP or Blank-SAP (control) was microinjected into the arcuate nucleus using stereotaxic surgery. After monitoring vaginal smears for 3-4 weeks, rats were ovariectomized and given 17β-estradiol and progesterone in a regimen that induced an afternoon LH surge. Rats were killed at the time of peak LH levels, and brains were harvested for NKB and dual labeled GnRH/Fos immunohistochemistry. In ovary-intact rats, ablation of KNDy neurons resulted in hypogonadotropic hypogonadism, characterized by low levels of serum LH, constant diestrus, ovarian atrophy with increased follicular atresia, and uterine atrophy. Surprisingly, the 17β-estradiol and progesterone-induced LH surge was 3 times higher in KNDy-ablated rats. Despite the marked increase in the magnitude of the LH surge, the number of GnRH or anterior ventral periventricular nucleus neurons expressing Fos was not significantly different between groups. Our studies show that KNDy neurons are essential for tonic levels of serum LH and estrous cyclicity and may play a role in limiting the magnitude of the LH surge.

Indexed as

AnimalsArcuate Nucleus of HypothalamusBody WeightDynorphinsEstradiolEstrous CycleFemaleHypogonadismKisspeptinsLuteinizing HormoneNeurokinin BNeuronsProgesteroneRatsRats, Sprague-DawleyDynorphinsEstradiolKisspeptinsLuteinizing HormoneNeurokinin BProgesterone

Identifiers

PMID26937713
PMCPMC4870865
OpenAlexW2291512884

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.