Evidence map›Paper›PMID 26076042›Full record

ArticleEndocrinology2015

Absent Progesterone Signaling in Kisspeptin Neurons Disrupts the LH Surge and Impairs Fertility in Female Mice.

Shannon B Z Stephens, Kristen P Tolson, Melvin L Rouse, Matthew C Poling, Minako K Hashimoto-Partyka, Pamela L Mellon, Alexander S Kauffman

Open access · bronzeAbstract read
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In one paragraph

Article in Endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
16.0field-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

62 citing papers in PubMed, 113 citations in OpenAlex.

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  19. Female sexual behavior is disrupted in a preclinical mouse model of PCOS via an attenuated hypothalamic nitric oxide pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
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2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Shannon B Z StephensDepartment of Reproductive Medicine (S.B.Z.S., K.P.T., M.L.R., M.C.P., P.L.M., A.S.K.), University of California, San Diego, La Jolla, California 92093; and Department of Molecular, Cellular, and Developmental Biology (M.K.H.-P.), University of California, Los Angeles, Los Angeles, California 90095.
Kristen P TolsonDepartment of Reproductive Medicine (S.B.Z.S., K.P.T., M.L.R., M.C.P., P.L.M., A.S.K.), University of California, San Diego, La Jolla, California 92093; and Department of Molecular, Cellular, and Developmental Biology (M.K.H.-P.), University of California, Los Angeles, Los Angeles, California 90095.
Melvin L RouseDepartment of Reproductive Medicine (S.B.Z.S., K.P.T., M.L.R., M.C.P., P.L.M., A.S.K.), University of California, San Diego, La Jolla, California 92093; and Department of Molecular, Cellular, and Developmental Biology (M.K.H.-P.), University of California, Los Angeles, Los Angeles, California 90095.
Matthew C PolingDepartment of Reproductive Medicine (S.B.Z.S., K.P.T., M.L.R., M.C.P., P.L.M., A.S.K.), University of California, San Diego, La Jolla, California 92093; and Department of Molecular, Cellular, and Developmental Biology (M.K.H.-P.), University of California, Los Angeles, Los Angeles, California 90095.
Minako K Hashimoto-PartykaDepartment of Reproductive Medicine (S.B.Z.S., K.P.T., M.L.R., M.C.P., P.L.M., A.S.K.), University of California, San Diego, La Jolla, California 92093; and Department of Molecular, Cellular, and Developmental Biology (M.K.H.-P.), University of California, Los Angeles, Los Angeles, California 90095.
Pamela L MellonDepartment of Reproductive Medicine (S.B.Z.S., K.P.T., M.L.R., M.C.P., P.L.M., A.S.K.), University of California, San Diego, La Jolla, California 92093; and Department of Molecular, Cellular, and Developmental Biology (M.K.H.-P.), University of California, Los Angeles, Los Angeles, California 90095.
Alexander S KauffmanDepartment of Reproductive Medicine (S.B.Z.S., K.P.T., M.L.R., M.C.P., P.L.M., A.S.K.), University of California, San Diego, La Jolla, California 92093; and Department of Molecular, Cellular, and Developmental Biology (M.K.H.-P.), University of California, Los Angeles, Los Angeles, California 90095.
University of California, San Diego · USUniversity of California, Los Angeles · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
Yeast Genetics and Stress Response Genes-BiomedicalP42ES010337 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2000 to 2022
$69.8M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
UCSD/SDSU IRACDAK12GM068524 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TREJO, JOANN · 2003 to 2025
$24.4M
The Interaction of Neuroendocrine Repro. Function and Metabolic SignalingU54HD012303 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MELLON, PAMELA L · 1999 to 2013
$18.0M
PROJECT 3 - Steroid-Metabolic Interactions In the Control of GnRH NeuronsU54HD028934 · NICHD · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI MARSHALL, JOHN C · 1998 to 2013
$16.5M
Testosterone-GnRH Frequency and the Evolution of PCOS in AdolescenceP50HD028934 · NICHD · UNIVERSITY OF VIRGINIA · PI HAISENLEDER, DANIEL J. · 2014 to 2018
$8.6M
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
Regulation of Vascular Function by Progesterone ReceptorR01HL074455 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI IRUELA-ARISPE, LUISA · 2003 to 2007
$1.9M
Neurosecretory Gene Expression in the HypothalamusR01HD072754 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MELLON, PAMELA L · 2012 to 2016
$1.7M
Neuroendocrine Actions of Androgens in Female ReproductionR01HD082567 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MELLON, PAMELA L · 2015 to 2019
$1.6M
NCI NIH HHS P30 CA023100NHLBI NIH HHS R01 HL074455NICHD NIH HHS F32 HD076606NICHD NIH HHS P50 HD012303NICHD NIH HHS P50 HD028934NICHD NIH HHS R01 HD065856NICHD NIH HHS R01 HD072754NICHD NIH HHS R01 HD082567NICHD NIH HHS T32 HD007203NICHD NIH HHS U54 HD012303NICHD NIH HHS U54-HD012303NICHD NIH HHS U54 HD028934NICHD NIH HHS U54HD28934NIDDK NIH HHS P30 DK063491NIEHS NIH HHS P42 ES010337NIGMS NIH HHS K12 GM068524
6 · The paper itself

Abstract

Kisspeptin, encoded by Kiss1, stimulates GnRH neurons to govern reproduction. In rodents, estrogen-sensitive kisspeptin neurons in the anterior ventral periventricular nucleus and neighboring periventricular nucleus are thought to mediate sex steroid-induced positive feedback induction of the preovulatory LH surge. These kisspeptin neurons coexpress estrogen and progesterone receptors and display enhanced neuronal activation during the LH surge. However, although estrogen regulation of kisspeptin neurons has been well studied, the role of progesterone signaling in regulating kisspeptin neurons is unknown. Here we tested whether progesterone action specifically in kisspeptin cells is essential for proper LH surge and fertility. We used Cre-lox technology to generate transgenic mice lacking progesterone receptors exclusively in kisspeptin cells (termed KissPRKOs). Male KissPRKOs displayed normal fertility and gonadotropin levels. In stark contrast, female KissPRKOs displayed earlier puberty onset and significant impairments in fertility, evidenced by fewer births and substantially reduced litter size. KissPRKOs also had fewer ovarian corpora lutea, suggesting impaired ovulation. To ascertain whether this reflects a defect in the ability to generate sex steroid-induced LH surges, females were exposed to an estradiol-positive feedback paradigm. Unlike control females, which displayed robust LH surges, KissPRKO females did not generate notable LH surges and expressed significantly blunted cfos induction in anterior ventral periventricular nucleus kisspeptin neurons, indicating that progesterone receptor signaling in kisspeptin neurons is required for normal kisspeptin neuronal activation and LH surges during positive feedback. Our novel findings demonstrate that progesterone signaling specifically in kisspeptin cells is essential for the positive feedback induction of normal LH surges, ovulation, and normal fertility in females.

Indexed as

FertilityAnimalsCorpus LuteumFeedback, PhysiologicalFemaleHypothalamus, AnteriorKisspeptinsLuteinizing HormoneMaleMice, Inbred C57BLMice, KnockoutPregnancyProgesteroneKiss1 protein, mouseKisspeptinsLuteinizing HormoneProgesterone

Identifiers

PMID26076042
PMCPMC4541622
OpenAlexW2181158448

What OpenQuestion holds

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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.