Testosterone improves muscle function of the extensor digitorum longus in rats with sepsis

Biosci Rep. 2020 Feb 28;40(2):BSR20193342. doi: 10.1042/BSR20193342.

Abstract

Among patients with intensive care unit-acquired weakness (ICUAW), skeletal muscle strength often decreases significantly. The present study aimed to explore the effects of testosterone propotionate on skeletal muscle using rat model of sepsis. Male SD rats were randomly divided into experimental group, model control group, sham operation group and blank control group. Rats in experimental group were given testosterone propionate two times a week, 10 mg/kg for 3 weeks. Maximal contraction force, fatigue index and cross-sectional area of the extensor digitorum longus (EDL) were measured. Myosin, IGF-1, p-AKT and p-mTOR levels in EDL were detected by Western blot. Histological changes of the testis and prostate were detected by hematoxylin and eosin staining. We found that maximal contraction force and fatigue index of EDL in experimental group were significantly higher than in model control group. Cross-sectional area of fast MHC muscle fiber of EDL in group was significantly higher than in model control group. The levels of myosin, IGF-1, p-AKT and p-mTOR of EDL in experimental group were significantly higher than in model control group. In addition, no testicle atrophy and prostate hyperplasia were detected in experimental group. In conclusion, these results suggest that testosterone propionate can significantly improve skeletal muscle strength, endurance and volume of septic rats, and the mechanism may be related to the activation of IGF-1/AKT pathway. Moreover, testosterone propionate with short duration does not cause testicular atrophy and prostate hyperplasia in septic rats. Therefore, testosterone propionate is a potential treatment for muscle malfunction in ICUAW patients.

Keywords: ICUAW; IGF-1; sepsis; skeletal muscle; testosterone propionate.

MeSH terms

  • Androgens / pharmacology*
  • Androgens / toxicity
  • Animals
  • Disease Models, Animal
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Muscle Contraction / drug effects*
  • Muscle Fatigue / drug effects
  • Muscle Strength / drug effects*
  • Muscle Weakness / drug therapy*
  • Muscle Weakness / etiology
  • Muscle Weakness / metabolism
  • Muscle Weakness / physiopathology
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiopathology
  • Myosins / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats, Sprague-Dawley
  • Sepsis / complications*
  • TOR Serine-Threonine Kinases / metabolism
  • Testosterone Propionate / pharmacology*
  • Testosterone Propionate / toxicity

Substances

  • Androgens
  • insulin-like growth factor-1, rat
  • Insulin-Like Growth Factor I
  • mTOR protein, rat
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Myosins
  • Testosterone Propionate