Muscle-derived myostatin is a major endocrine driver of follicle-stimulating hormone synthesis
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.
Authors
- Seth J. Karp (ORCID: https://orcid.org/0000-0002-5266-1025)
- Ulrich Boehm (ORCID: https://orcid.org/0000-0003-2436-6907)
- Emilie Brûlé (ORCID: https://orcid.org/0000-0001-6149-6861)
- Frederique Ruf-Zamojski
- Kelly L. Walton (ORCID: https://orcid.org/0000-0003-0627-2958)
- Yeu‐Farn Lin (ORCID: https://orcid.org/0000-0002-2880-4532)
- Hailey Schultz (ORCID: https://orcid.org/0009-0006-5906-7148)
- Gloria H. Su (ORCID: https://orcid.org/0000-0002-5158-6019)
- Stuart C. Sealfon (ORCID: https://orcid.org/0000-0001-5791-1217)
- Adam Hagg (ORCID: https://orcid.org/0000-0001-7951-743X)
- Daniel J. Bernard (ORCID: https://orcid.org/0000-0001-5365-5586)
- Gauthier Schang
- Luisina Ongaro (ORCID: https://orcid.org/0000-0002-5449-2894)
- Nabil G. Seidah (ORCID: https://orcid.org/0000-0001-6503-9342)
- Roselyne Castonguay
- Ying Wáng (ORCID: https://orcid.org/0000-0002-8863-554X)
- Xiang Zhou (ORCID: https://orcid.org/0000-0002-9344-3294)
- Se‐Jin Lee (ORCID: https://orcid.org/0000-0003-1523-0389)
- Yewei Liu (ORCID: https://orcid.org/0000-0001-6596-815X)
- Evan R. S. Buddle (ORCID: https://orcid.org/0009-0000-9529-4918)
- Kevin C. Ray
- Ziyue Zhou (ORCID: https://orcid.org/0000-0003-4725-7543)
Institutions
- Cedars-Sinai Medical Center (US)
- University of Connecticut (US)
- The University of Queensland (AU)
- Columbia University Irving Medical Center (US)
- Acceleron Pharma (United States) (US)
- Jackson Laboratory (US)
- Montreal Clinical Research Institute (CA)
- McGill University (CA)
- Vanderbilt University Medical Center (US)
- Saarland University (DE)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Science
- Published
- 2025-01-16
- DOI
- https://doi.org/10.1126/science.adi4736
- Citations
- 37
- Primary Topic
- Muscle Physiology and Disorders
- Type
- article
- Field-Weighted Citation Impact
- 29.82
Funders
- U.S. Department of Health and Human Services
- Eli Lilly and Company
- AstraZeneca
- Michigan State University
- University of Washington
- University of Cincinnati
- McGill University
- Regeneron Pharmaceuticals
- Cedars-Sinai Medical Center
- Novo Nordisk
- Institut de Recherche Clinique De Montréal
- National Institutes of Health
- College of Engineering, Michigan State University
- University of California, San Diego
- Irving Medical Center, Columbia University
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada