Androgen-mediated regulation of skeletal muscle protein balance

Abstract

Androgens significantly alter muscle mass in part by shifting protein balance in favor of net protein accretion. During various atrophic conditions, the clinical impact of decreased production or bioavailability of androgens (termed hypogonadism) is important as a loss of muscle mass is intimately linked with survival outcome. While androgen replacement therapy increases muscle mass in part by restoring protein balance, this is not a comprehensive treatment option due to potential side effects. Therefore, an understanding of the mechanisms by which androgens alter protein balance is needed for the development of androgen-independent therapies. While the data in humans suggest androgens alter protein balance (both synthesis and breakdown) in the fasted metabolic state, a predominant molecular mechanism(s) behind this observation is still lacking. This failure is likely due in part to inconsistent experimental design between studies including failure to control nutrient/feeding status, the method of altering androgens, and the model systems utilized.

Keywords: Anabolic; Atrophy; Autophagy; Catabolic; Hypertrophy; Testosterone.

FIGURE 1

Theoretical model by which androgens alter muscle protein balance at differing androgen concentrations.

FIGURE 2

Summary of the proposed mechanisms by which androgens alter muscle protein balance.