IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-35243-z.html
   My bibliography  Save this article

Definition of the estrogen negative feedback pathway controlling the GnRH pulse generator in female mice

Author

Listed:
  • H. James McQuillan

    (University of Otago School of Biomedical Sciences
    University of Otago School of Biomedical Sciences)

  • Jenny Clarkson

    (University of Otago School of Biomedical Sciences
    University of Otago School of Biomedical Sciences)

  • Alexia Kauff

    (University of Otago School of Biomedical Sciences)

  • Su Young Han

    (University of Otago School of Biomedical Sciences
    University of Otago School of Biomedical Sciences
    University of Cambridge)

  • Siew Hoong Yip

    (University of Otago School of Biomedical Sciences
    University of Otago School of Biomedical Sciences)

  • Isaiah Cheong

    (University of Otago School of Biomedical Sciences
    University of Otago School of Biomedical Sciences)

  • Robert Porteous

    (University of Otago School of Biomedical Sciences
    University of Otago School of Biomedical Sciences)

  • Alison K. Heather

    (University of Otago School of Biomedical Sciences)

  • Allan E. Herbison

    (University of Otago School of Biomedical Sciences
    University of Otago School of Biomedical Sciences
    University of Cambridge)

Abstract

The mechanisms underlying the homeostatic estrogen negative feedback pathway central to mammalian fertility have remained unresolved. Direct measurement of gonadotropin-releasing hormone (GnRH) pulse generator activity in freely behaving mice with GCaMP photometry demonstrated striking estradiol-dependent plasticity in the frequency, duration, amplitude, and profile of pulse generator synchronization events. Mice with Cre-dependent deletion of ESR1 from all kisspeptin neurons exhibited pulse generator activity identical to that of ovariectomized wild-type mice. An in vivo CRISPR-Cas9 approach was used to knockdown ESR1 expression selectively in arcuate nucleus (ARN) kisspeptin neurons. Mice with >80% deletion of ESR1 in ARN kisspeptin neurons exhibited the ovariectomized pattern of GnRH pulse generator activity and high frequency LH pulses but with very low amplitude due to reduced responsiveness of the pituitary. Together, these studies demonstrate that estrogen utilizes ESR1 in ARN kisspeptin neurons to achieve estrogen negative feedback of the GnRH pulse generator in mice.

Suggested Citation

  • H. James McQuillan & Jenny Clarkson & Alexia Kauff & Su Young Han & Siew Hoong Yip & Isaiah Cheong & Robert Porteous & Alison K. Heather & Allan E. Herbison, 2022. "Definition of the estrogen negative feedback pathway controlling the GnRH pulse generator in female mice," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35243-z
    DOI: 10.1038/s41467-022-35243-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35243-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-35243-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Jose M. Ramos-Pittol & Isabel Fernandes-Freitas & Alexandra Milona & Stephen M. Manchishi & Kara Rainbow & Brian Y. H. Lam & John A. Tadross & Anthony Beucher & William H. Colledge & Inês Cebola & Kev, 2023. "Dax1 modulates ERα-dependent hypothalamic estrogen sensing in female mice," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35243-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.