Testosterone and trenbolone enanthate increase mature myostatin protein expression despite increasing skeletal muscle hypertrophy and satellite cell number in rodent muscle

Andrologia. 2017 Apr;49(3). doi: 10.1111/and.12622. Epub 2016 Jun 1.

Abstract

The androgen-induced alterations in adult rodent skeletal muscle fibre cross-sectional area (fCSA), satellite cell content and myostatin (Mstn) were examined in 10-month-old Fisher 344 rats (n = 41) assigned to Sham surgery, orchiectomy (ORX), ORX + testosterone (TEST; 7.0 mg week-1 ) or ORX + trenbolone (TREN; 1.0 mg week-1 ). After 29 days, animals were euthanised and the levator ani/bulbocavernosus (LABC) muscle complex was harvested for analyses. LABC muscle fCSA was 102% and 94% higher in ORX + TEST and ORX + TREN compared to ORX (p < .001). ORX + TEST and ORX + TREN increased satellite cell numbers by 181% and 178% compared to ORX, respectively (p < .01), with no differences between conditions for myonuclear number per muscle fibre (p = .948). Mstn protein was increased 159% and 169% in the ORX + TEST and ORX + TREN compared to ORX (p < .01). pan-SMAD2/3 protein was ~30-50% greater in ORX compared to SHAM (p = .006), ORX + TEST (p = .037) and ORX + TREN (p = .043), although there were no between-treatment effects regarding phosphorylated SMAD2/3. Mstn, ActrIIb and Mighty mRNAs were lower in ORX, ORX + TEST and ORX + TREN compared to SHAM (p < .05). Testosterone and trenbolone administration increased muscle fCSA and satellite cell number without increasing myonuclei number, and increased Mstn protein levels. Several genes and signalling proteins related to myostatin signalling were differentially regulated by ORX or androgen therapy.

Keywords: androgen; cell cycle; satellite cells; selective androgen receptor modulator; steroids.

MeSH terms

  • Activin Receptors, Type II / metabolism
  • Anabolic Agents / administration & dosage
  • Anabolic Agents / pharmacology*
  • Androgens / administration & dosage
  • Androgens / pharmacology*
  • Animals
  • Cell Count
  • Cell Differentiation / drug effects
  • Cell Enlargement / drug effects
  • Male
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / growth & development
  • Muscle, Skeletal / metabolism
  • Myostatin / metabolism*
  • Orchiectomy / adverse effects
  • Rats
  • Rats, Inbred F344
  • Satellite Cells, Skeletal Muscle / cytology
  • Satellite Cells, Skeletal Muscle / drug effects*
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Testis / surgery
  • Testosterone / administration & dosage
  • Testosterone / pharmacology*
  • Trenbolone Acetate / administration & dosage
  • Trenbolone Acetate / pharmacology*

Substances

  • Anabolic Agents
  • Androgens
  • Mstn protein, rat
  • Myostatin
  • Smad2 Protein
  • Smad2 protein, rat
  • Smad3 Protein
  • Smad3 protein, rat
  • Testosterone
  • Activin Receptors, Type II
  • activin receptor type II-B
  • Trenbolone Acetate