Evidence map›Paper›PMID 34379733›Full record

ArticleEndocrinology2021

Progesterone Receptors in AVPV Kisspeptin Neurons Are Sufficient for Positive Feedback Induction of the LH Surge.

Margaret A Mohr, Lourdes A Esparza, Paige Steffen, Paul E Micevych, Alexander S Kauffman

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
5.4field-weighted citation impact, top 4% 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

25 citing papers in PubMed, 34 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
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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 2 institutions in 1 country.

Margaret A MohrDepartment of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, Los Angeles, CA 90095, USA.
Lourdes A EsparzaDepartment of OBGYN and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Paige SteffenDepartment of OBGYN and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Paul E MicevychDepartment of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, Los Angeles, CA 90095, USA.
Alexander S KauffmanDepartment of OBGYN and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92093, USA.ORCID 0000-0001-8631-6097
University of California San Diego · USUniversity of California, Los Angeles · US

Funding

The Role of FSH in Female InfertilityP50HD012303 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MELLON, PAMELA L · 1985 to 2020
$7.5M
Physiology of Hypothalamic Neurosteroidal ProgesteroneR01HD042635 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MICEVYCH, PAUL E · 2003 to 2019
$4.8M
Neurosecretory Gene Expression in the HypothalamusR01HD100580 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MELLON, PAMELA L · 2020 to 2024
$2.7M
CRR LIGAND ASSAY AND ANALYSIS CORER24HD102061 · NICHD · UNIVERSITY OF VIRGINIA · PI HAISENLEDER, DANIEL J. · 2019 to 2023
$2.2M
Neuroendocrine regulation of puberty and reproductive developmentR01HD090161 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KAUFFMAN, ALEXANDER S · 2017 to 2021
$1.9M
Estrogen Responsiveness Of Pubertally Born Hypothalamic Astrocytes.F32HD097965 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MOHR, MARGARET · 2019 to 2020
$133k
NICHD NIH HHS F32 HD097965NICHD NIH HHS P50 HD012303NICHD NIH HHS R01 HD042635NICHD NIH HHS R01 HD090161NICHD NIH HHS R01 HD100580NICHD NIH HHS R24 HD102061
6 · The paper itself

Abstract

Kisspeptin, encoded by Kiss1, stimulates gonadotropin-releasing hormone neurons to govern reproduction. In female rodents, estrogen-sensitive kisspeptin neurons in the rostral anteroventral periventricular (AVPV) hypothalamus are thought to mediate estradiol (E2)-induced positive feedback induction of the preovulatory luteinizing hormone (LH) surge. AVPV kisspeptin neurons coexpress estrogen and progesterone receptors (PGRs) and are activated during the LH surge. While E2 effects on kisspeptin neurons have been well studied, progesterone's regulation of kisspeptin neurons is less understood. Using transgenic mice lacking PGR exclusively in kisspeptin cells (termed KissPRKOs), we previously demonstrated that progesterone action specifically in kisspeptin cells is essential for ovulation and normal fertility. Unlike control females, KissPRKO females did not generate proper LH surges, indicating that PGR signaling in kisspeptin cells is required for positive feedback. However, because PGR was knocked out from all kisspeptin neurons in the brain, that study was unable to determine the specific kisspeptin population mediating PGR action on the LH surge. Here, we used targeted Cre-mediated adeno-associated virus (AAV) technology to reintroduce PGR selectively into AVPV kisspeptin neurons of adult KissPRKO females, and tested whether this rescues occurrence of the LH surge. We found that targeted upregulation of PGR in kisspeptin neurons exclusively in the AVPV is sufficient to restore proper E2-induced LH surges in KissPRKO females, suggesting that this specific kisspeptin population is a key target of the necessary progesterone action for the surge. These findings further highlight the critical importance of progesterone signaling, along with E2 signaling, in the positive feedback induction of LH surges and ovulation.

Indexed as

AnimalsEstradiolFeedback, PhysiologicalFemaleHypothalamus, AnteriorKisspeptinsLuteinizing HormoneMiceMice, KnockoutNeuronsProgesteroneReceptors, ProgesteroneUp-RegulationEstradiolKisspeptinsLuteinizing HormoneProgesteroneReceptors, ProgesteroneAVPVGnRHKiss1KisspeptinLH surgeovulationpositive feedbackprogesteroneRP3V

Identifiers

PMID34379733
PMCPMC8423423
OpenAlexW3188683786

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.