Muscle-derived myostatin is a major endocrine driver of follicle-stimulating hormone synthesis

  • Luisina Ongaro
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
  • Xiang Zhou
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
  • Ying Wang
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
  • Hailey Schultz
    Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
  • Ziyue Zhou
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
  • Evan R. S. Buddle
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
  • Emilie Brûlé
    Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
  • Yeu-Farn Lin
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
  • Gauthier Schang
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
  • Adam Hagg
    School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia.
  • Roselyne Castonguay
    Discovery Group, Acceleron Pharma Inc., Rahway, NJ, USA.
  • Yewei Liu
    The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Gloria H. Su
    Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
  • Nabil G. Seidah
    Laboratory of Biochemical Neuroendocrinology, Montreal Clinical Research Institute (IRCM)–University of Montreal, Montreal, Quebec, Canada.
  • Kevin C. Ray
    Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Seth J. Karp
    Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Ulrich Boehm
    Department of Pharmacology and Toxicology, University of Saarland School of Medicine, Homburg, Germany.
  • Frederique Ruf-Zamojski
    Cedars-Sinai Medical Center, Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Los Angeles, CA, USA.
  • Stuart C. Sealfon
    Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Kelly L. Walton
    School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia.
  • Se-Jin Lee
    The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • Daniel J. Bernard
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.

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説明

<jats:p>Myostatin is a paracrine myokine that regulates muscle mass in a variety of species, including humans. In this work, we report a functional role for myostatin as an endocrine hormone that directly promotes pituitary follicle-stimulating hormone (FSH) synthesis and thereby ovarian function in mice. Previously, this FSH-stimulating role was attributed to other members of the transforming growth factor–β family, the activins. Our results both challenge activin’s eponymous role in FSH synthesis and establish an unexpected endocrine axis between skeletal muscle and the pituitary gland. Our data also suggest that efforts to antagonize myostatin to increase muscle mass may have unintended consequences on fertility.</jats:p>

収録刊行物

  • Science

    Science 387 (6731), 329-336, 2025-01-17

    American Association for the Advancement of Science (AAAS)

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