Overexpression of glucocorticoid receptor β enhances myogenesis and reduces catabolic gene expression

Terry D. Hinds, Bailey Peck, Evan Shek, Steven Stroup, Jennifer Hinson, Susan Arthur, Joseph S. Marino

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Unlike the glucocorticoid receptor α (GRα), GR β (GRβ) has a truncated ligand-binding domain that prevents glucocorticoid binding, implicating GRα as the mediator of glucocorticoid-induced skeletal muscle loss. Because GRβ causes glucocorticoid resistance, targeting GRβ may be beneficial in impairing muscle loss as a result of GRα activity. The purpose of this study was to determine how the overexpression of GRβ affects myotube formation and dexamethasone (Dex) responsiveness. We measured GR isoform expression in C2C12 muscle cells in response to Dex and insulin, and through four days of myotube formation. Next, lentiviral-mediated overexpression of GRβ in C2C12 was performed, and these cells were characterized for cell fusion and myotube formation, as well as sensitivity to Dex via the expression of ubiquitin ligases. GRβ overexpression increased mRNA levels of muscle regulatory factors and enhanced proliferation in myoblasts. GRβ overexpressing myotubes had an increased fusion index. Myotubes overexpressing GRβ had lower forkhead box O3 (Foxo3a) mRNA levels and a blunted muscle atrophy F-box/Atrogen-1 (MAFbx) and muscle ring finger 1 (MuRF1) response to Dex. We showed that GRβ may serve as a pharmacological target for skeletal muscle growth and protection from glucocorticoid-induced catabolic signaling. Increasing GRβ levels in skeletal muscle may cause a state of glucocorticoid resistance, stabilizing muscle mass during exposure to high doses of glucocorticoids.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2016

Bibliographical note

Publisher Copyright:
© 2016 by the authors; licensee MDPI, Basel, Switzerland.

Keywords

  • Atrophy 6
  • Dexamethasone 9
  • GRα 5
  • GRβ 4
  • Glucocorticoid receptor α 2
  • Glucocorticoid receptor β 3
  • MAFbx 7
  • MuRF1 8
  • Myogenesis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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