Resistance Training Ameliorates Finasteride-Induced Disturbance in Protein Homeostasis in Skeletal Muscle of Rats

Abstract

PURPOSE Finasteride is a competitive inhibitor of 5-alpha reductase type 2 enzyme that is commonly used to treat benign prostatic hyperplasia and male pattern hair loss. It is not clear about the synergistic effects of finasteride and resistance training on protein homeostasis in androgen-target tissue such as skeletal muscle. Thus, the purpose of this study was to investigate the effects of 8-week finasteride and resistance exercise training on protein synthesis and autophagic degradation in rat skeletal muscle. METHODS Forty-eight male wild-type Sprague Dawley rats (8weeks old) were randomly assigned into 4 groups: (1) sedentary control, (2) finasteride, (3) exercise, and (4) exercise plus finasteride. Rats of the finasteride group received finasteride, dissolved in corn oil (10 mg/kg) by oral gavage. Rats of the exercise group climbed a 1-m ladder inclined at 85° every 3 days for 8 weeks as a means of resistance exercise. They climbed the ladder 8 times with the load of 50%, 75%, 90%, and 100% of its body weight. Rates of the exercise plus finasteride group were given both interventions. We assessed autophagy flux, protein synthesis (mTOR signaling and translation rate using the SUnSET assay), and muscular functions before and after 8-weeks of intervention, and performed one-way ANOVA to determine pre-post differences in each group. RESULTS The finasteride treatment significantly reduced protein synthesis while activating autophagic degradation in skeletal muscle of rats. The exercise training increased both protein synthesis and autophagic degradation. The combined treatments decreased both protein synthesis and autophagy flux in the skeletal muscle (p<0.05). CONCLUSIONS Eight weeks of finasteride treatment appears to disturb the protein homeostasis, which is viewed as a balance of protein synthesis and degradation through the reduction in protein synthesis and activation in autophagic degradation simultaneously in skeletal muscle. Resistance exercise appears to alleviate the disruption of protein homeostasis induced by finasteride treatment.

Keywords

• finasteride
• autophagy
• autophagic flux
• protein homeostasis
• skeletal muscle