IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-018-08046-4.html
   My bibliography  Save this article

Estrogen signaling in arcuate Kiss1 neurons suppresses a sex-dependent female circuit promoting dense strong bones

Author

Listed:
  • Candice B. Herber

    (University of California San Francisco)

  • William C. Krause

    (University of California San Francisco)

  • Liping Wang

    (University of California San Francisco)

  • James R. Bayrer

    (University of California San Francisco)

  • Alfred Li

    (University of California San Francisco)

  • Matthew Schmitz

    (School of Medicine University of California San Francisco)

  • Aaron Fields

    (School of Medicine Mission Bay Campus University of California San Francisco)

  • Breanna Ford

    (University of California)

  • Zhi Zhang

    (University of California Los Angeles)

  • Michelle S. Reid

    (University of California Los Angeles)

  • Daniel K. Nomura

    (University of California)

  • Robert A. Nissenson

    (University of California San Francisco)

  • Stephanie M. Correa

    (University of California San Francisco
    University of California Los Angeles)

  • Holly A. Ingraham

    (University of California San Francisco)

Abstract

Central estrogen signaling coordinates energy expenditure, reproduction, and in concert with peripheral estrogen impacts skeletal homeostasis in females. Here, we ablate estrogen receptor alpha (ERα) in the medial basal hypothalamus and find a robust bone phenotype only in female mice that results in exceptionally strong trabecular and cortical bones, whose density surpasses other reported mouse models. Stereotaxic guided deletion of ERα in the arcuate nucleus increases bone mass in intact and ovariectomized females, confirming the central role of estrogen signaling in this sex-dependent bone phenotype. Loss of ERα in kisspeptin (Kiss1)-expressing cells is sufficient to recapitulate the bone phenotype, identifying Kiss1 neurons as a critical node in this powerful neuroskeletal circuit. We propose that this newly-identified female brain-to-bone pathway exists as a homeostatic regulator diverting calcium and energy stores from bone building when energetic demands are high. Our work reveals a previously unknown target for treatment of age-related bone disease.

Suggested Citation

  • Candice B. Herber & William C. Krause & Liping Wang & James R. Bayrer & Alfred Li & Matthew Schmitz & Aaron Fields & Breanna Ford & Zhi Zhang & Michelle S. Reid & Daniel K. Nomura & Robert A. Nissenso, 2019. "Estrogen signaling in arcuate Kiss1 neurons suppresses a sex-dependent female circuit promoting dense strong bones," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08046-4
    DOI: 10.1038/s41467-018-08046-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-08046-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-08046-4?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. Tom W. Andrew & Lauren S. Koepke & Yuting Wang & Michael Lopez & Holly Steininger & Danielle Struck & Tatiana Boyko & Thomas H. Ambrosi & Xinming Tong & Yuxi Sun & Gunsagar S. Gulati & Matthew P. Murp, 2022. "Sexually dimorphic estrogen sensing in skeletal stem cells controls skeletal regeneration," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Zhenxi Li & Xinghai Yang & Ruifeng Fu & Zhipeng Wu & Shengzhao Xu & Jian Jiao & Ming Qian & Long Zhang & Chunbiao Wu & Tianying Xie & Jiqiang Yao & Zhixiang Wu & Wenjun Li & Guoli Ma & Yu You & Yihua , 2024. "Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src," Nature Communications, Nature, vol. 15(1), pages 1-17, 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:10:y:2019:i:1:d:10.1038_s41467-018-08046-4. 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.