Estrogen Regulates the Satellite Cell Compartment in Females
Brittany C. Collins,
Robert W. Arpke,
Alexie A. Larson,
Cory W. Baumann,
Ning Xie,
Christine A. Cabelka,
Nardina L. Nash,
Hanna-Kaarina Juppi,
Eija K. Laakkonen,
Sarianna Sipilä,
Vuokko Kovanen,
Espen E. Spangenburg,
Michael Kyba,
Dawn A. Lowe
Affiliations
Brittany C. Collins
Divisions of Rehabilitation Science and Physical Therapy, Department of Rehabilitation Medicine, Medical School, University of Minnesota, Minneapolis, MN, USA
Robert W. Arpke
Lillehei Heart Institute and Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, MN, USA
Alexie A. Larson
Department of Integrative Biology and Physiology, Medical School, University of Minnesota, Minneapolis, MN, USA
Cory W. Baumann
Divisions of Rehabilitation Science and Physical Therapy, Department of Rehabilitation Medicine, Medical School, University of Minnesota, Minneapolis, MN, USA
Ning Xie
Lillehei Heart Institute and Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, MN, USA
Christine A. Cabelka
Divisions of Rehabilitation Science and Physical Therapy, Department of Rehabilitation Medicine, Medical School, University of Minnesota, Minneapolis, MN, USA
Nardina L. Nash
Divisions of Rehabilitation Science and Physical Therapy, Department of Rehabilitation Medicine, Medical School, University of Minnesota, Minneapolis, MN, USA
Hanna-Kaarina Juppi
Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
Eija K. Laakkonen
Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
Sarianna Sipilä
Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
Vuokko Kovanen
Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
Espen E. Spangenburg
East Carolina Diabetes and Obesity Institute, Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, USA
Michael Kyba
Lillehei Heart Institute and Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, MN, USA
Dawn A. Lowe
Divisions of Rehabilitation Science and Physical Therapy, Department of Rehabilitation Medicine, Medical School, University of Minnesota, Minneapolis, MN, USA; Corresponding author
Summary: Skeletal muscle mass, strength, and regenerative capacity decline with age, with many measures showing a greater deterioration in females around the time estrogen levels decrease at menopause. Here, we show that estrogen deficiency severely compromises the maintenance of muscle stem cells (i.e., satellite cells) as well as impairs self-renewal and differentiation into muscle fibers. Mechanistically, by hormone replacement, use of a selective estrogen-receptor modulator (bazedoxifene), and conditional estrogen receptor knockout, we implicate 17β-estradiol and satellite cell expression of estrogen receptor α and show that estrogen signaling through this receptor is necessary to prevent apoptosis of satellite cells. Early data from a biopsy study of women who transitioned from peri- to post-menopause are consistent with the loss of satellite cells coincident with the decline in estradiol in humans. Together, these results demonstrate an important role for estrogen in satellite cell maintenance and muscle regeneration in females. : Collins et al. show the loss of estrogen in female mice and post-menopausal women leads to a decrease in skeletal muscle stem cells. Using muscle stem cell-specific mutants, it was demonstrated that ERα is necessary for satellite cell maintenance, self-renewal, and protection from apoptosis, thereby promoting optimal muscle regeneration. Keywords: estradiol, muscle stem cells, ovarian hormones, quiescence, skeletal muscle
