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Dax1 modulates ERα-dependent hypothalamic estrogen sensing in female mice

Author

Listed:
  • Jose M. Ramos-Pittol

    (University of Innsbruck)

  • Isabel Fernandes-Freitas

    (Imperial College London)

  • Alexandra Milona

    (Imperial College London)

  • Stephen M. Manchishi

    (Cambridge University)

  • Kara Rainbow

    (Cambridge University)

  • Brian Y. H. Lam

    (Cambridge University)

  • John A. Tadross

    (Cambridge University
    Cambridge University Hospitals NHS Foundation Trust)

  • Anthony Beucher

    (Imperial College London)

  • William H. Colledge

    (Cambridge University)

  • Inês Cebola

    (Imperial College London)

  • Kevin G. Murphy

    (Imperial College London)

  • Irene Miguel-Aliaga

    (Imperial College London
    MRC London Institute of Medical Sciences)

  • Giles S. H. Yeo

    (Cambridge University)

  • Waljit S. Dhillo

    (Imperial College London)

  • Bryn M. Owen

    (Imperial College London)

Abstract

Coupling the release of pituitary hormones to the developmental stage of the oocyte is essential for female fertility. It requires estrogen to restrain kisspeptin (KISS1)-neuron pulsatility in the arcuate hypothalamic nucleus, while also exerting a surge-like effect on KISS1-neuron activity in the AVPV hypothalamic nucleus. However, a mechanistic basis for this region-specific effect has remained elusive. Our genomic analysis in female mice demonstrate that some processes, such as restraint of KISS1-neuron activity in the arcuate nucleus, may be explained by region-specific estrogen receptor alpha (ERα) DNA binding at gene regulatory regions. Furthermore, we find that the Kiss1-locus is uniquely regulated in these hypothalamic nuclei, and that the nuclear receptor co-repressor NR0B1 (DAX1) restrains its transcription specifically in the arcuate nucleus. These studies provide mechanistic insight into how ERα may control the KISS1-neuron, and Kiss1 gene expression, to couple gonadotropin release to the developmental stage of the oocyte.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38618-y
    DOI: 10.1038/s41467-023-38618-y
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    References listed on IDEAS

    as
    1. Melissa J. Fullwood & Mei Hui Liu & You Fu Pan & Jun Liu & Han Xu & Yusoff Bin Mohamed & Yuriy L. Orlov & Stoyan Velkov & Andrea Ho & Poh Huay Mei & Elaine G. Y. Chew & Phillips Yao Hui Huang & Willem, 2009. "An oestrogen-receptor-α-bound human chromatin interactome," Nature, Nature, vol. 462(7269), pages 58-64, November.
    2. 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.
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