title: Testosterone inhibits transforming growth factor-β signaling during myogenic differentiation and proliferation of mouse satellite cells: potential role of follistatin in mediating testosterone action.
abstract: Testosterone (T) administration is associated with increased satellite cell number and skeletal muscle hypertrophy, although there is considerable heterogeneity in the response of different skeletal muscle groups to T in vivo. We investigated the effects of T on the growth and differentiation of satellite cells isolated from levator ani (LA) and gastrocnemius (gastroc) muscles. T up regulated follistatin (Fst) expression, but down regulated the mRNA and protein expression of a number of genes in the transforming growth factor-beta (TGF-β)-signaling pathway. Inhibition of Fst expression by small interfering RNA (siRNA) inhibited myogenic differentiation and blocked the pro-myogenic effects of T. Treatment of satellite cells with T or Fst up regulated the expression of Pax7 and PCNA, and increased their proliferation. T and Fst blocked TGF-β induced inhibition of growth and myogenic differentiation and down regulated TGF-β-dependent transcriptome in both LA and gastroc cells. We conclude that T stimulation of satellite cell proliferation and myogenic differentiation are associated with up regulation of Fst and inhibition of TGF-β-signaling.
authors.affiliation: Division of Endocrinology and Metabolism, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, United States. melissabraga@cdrewu.edu
authors.forename: Melissa
authors.initials: M
authors.lastname: Braga
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
authors.forename: Ravi
authors.initials: R
authors.lastname: Jasuja
authors.forename: Shehla
authors.initials: S
authors.lastname: Pervin
authors.forename: Rajan
authors.initials: R
authors.lastname: Singh
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D038681:Follistatin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D061251:Primary Cell Culture; D011944:Receptors, Androgen / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D019485:Bone Morphogenetic Proteins; D038681:Follistatin; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D011944:Receptors, Androgen; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D013739:Testosterone; D018995:Myosin Heavy Chains