Impaired skeletal muscle development and function in male, but not female, genomic androgen receptor knockout mice

Abstract

To identify mechanisms of anabolic androgen action in muscle, we generated male and female genomic androgen receptor (AR) knockout (ARKO) mice, and characterized muscle mass, contractile function, and gene expression. Muscle mass is decreased in ARKO males, but normal in ARKO females. The levator ani muscle, which fails to develop in normal females, is also absent in ARKO males. Force production is decreased from fast-twitch ARKO male muscle, and slow-twitch muscle has increased fatigue resistance. Microarray analysis shows up-regulation of genes encoding slow-twitch muscle contractile proteins. Real-time PCR confirms that expression of genes encoding polyamine biosynthetic enzymes, ornithin..