However, the primary tissue of interest, relative to AAS use for physique or performance improvement, is skeletal muscle. Skeletal muscle includes the familiar biceps, pecs, quads and other muscles that aid in movement. Two other classes of muscle include smooth muscle, which is present in the gut and blood vessels, the second being cardiac (heart) muscle. AAS may affect these other two types, particularly the heart, but these effects are outside the scope of this article. Skeletal muscle does not contain detectable levels of 5a-reductase, but does have significant aromatase activity.7,8 Thus, testosterone is the primary androgen responsible for muscle hypertrophy; the role of estrogen in skeletal muscle remains unknown at this time.

            Testosterone affects the muscle cell by activating genomic and non-genomic targets. The genomic effects of testosterone involve the classically understood mechanism of testosterone entering the cytoplasm (the inside of the cell), binding with an androgen receptor (AR) and traveling together into the nucleus of the cell. Once in the nucleus, the testosterone-AR complex turns on or off specific genes (segments of DNA), resulting in muscle cell hypertrophy (growth). However, the genomic signaling is not so simple. Every cell contains varying concentrations of co-regulators which can promote or inhibit the ability of the testosterone-AR complex to activate genes.9 Unfortunately, this is an area that is poorly understood, so until further research emerges, the relative importance of these co-regulators remains unclear.

            Testosterone can also affect receptors and enzymes directly. Receptors imbedded in the membrane or in the cytoplasm can be activated by testosterone and have a near-immediate effect on cell function and behavior.10,11 This is most evident in mating-related or risk-taking behaviors. Researchers at Lehigh University recently published a study demonstrating that the reflexive testosterone release of male mice in mating situations directly and rapidly increased arousal and mounting of a receptive female.12 In other words, when a new, sexually receptive female was introduced into a male mouse’s pen, his body produced a surge of testosterone that made him more quickly get aroused and mount the female. Additionally, reductions in anxiety and pain perception have been reported, as well as increases in behavior-reward association.13 This effect has not been as directly measured in humans, but advertising executives have been aware of a similar phenomenon in men for centuries. Sociologists and neurologists have confirmed that men will take greater sexual and financial risks (i.e., failing to use a condom, gambling) when sexually aroused or even when simply presented with an erotic image.14,15