Direct and Indirect Anabolic Effects

Although testosterone has been isolated, synthesized, and actively experimented with for many decades now, there is still some debate today as to exactly how steroids affect muscle mass. At this point in time, the primary mode of anabolic action with all anabolic/androgenic steroids is understood to be direct activation of the cellular androgen receptor and increases in protein synthesis. As follows, if we are able to increase our androgen level from an external source by supplementing testosterone or a similar anabolic steroid, we can greatly enhance the rate in which protein is retained by the muscles.

This is clearly the primary cause for muscle growth with all anabolic/androgenic steroids. As our hormone levels increase, so does androgen receptor activation, and ultimately the rate of protein synthesis. But other indirect mechanisms could possibly affect muscle growth outside of the normally understood androgen action on protein synthesis. An indirect mechanism is one that is not brought about by activation of the androgen receptor, but the affect androgens might have on other hormones, or even the release of locally acting hormones or growth promoters inside cells (perhaps mediated by other membrane bound receptors).
We must remember also that muscle mass disposition involves not only protein synthesis, but also other factors such as tissue nutrient transport and protein breakdown. We need to look at androgenic interaction with these factors as well to get a complete picture. Concerning the first possibility, we note that studies with testosterone suggest that this hormone does not increase tissue amino acid transport. This fact probably explains the profound synergy bodybuilders have noted in recent years with insulin, a hormone that strongly increases transport of nutrients into muscle cells. But regarding protein breakdown, we do see a second important pathway in which androgens might affect muscle growth.

Anti-Glucocorticoid Effect of Testosterone

Testosterone (and synthetic anabolic/androgenic steroids) may help to increase mass and strength by having an anticatabolic effect on muscle cells. Considered one of the most important indirect mechanisms of androgen action, these hormones are shown to affect the actions of another type of steroid hormone in the body, glucocorticoids (cortisol is the primary representative of this group). Glucocorticoid hormones actually have the exact opposite effect on the muscle cell than androgens, namely sending an order to release stored protein. This process is referred to as catabolism, and represents a breaking down of muscle tissue. Muscle growth is achieved when the anabolic effects of testosterone are more pronounced overall than the degenerative effects of cortisol. With intense training and a proper diet, the body will typically store more protein than it removes, but this underlying battle is always constant. When administering anabolic steroids, however, a much higher androgen level can place glucocorticoids at a notable disadvantage. With their effect reduced, fewer cells will be given a message to release protein, and more will be accumulated in the long run.

The primary mechanism believed to bring this effect out is androgen displacement of glucocorticoids bound to the glucocorticoid receptor. In fact, in-vitro studies have supported this notion by demonstrating that testosterone has a very high affinity for this receptor, and further suggesting that some of its anabolic activity is directly mediated through this action. It is also suggested that androgens may indirectly interfere with DNA binding to the glucocorticoid response element. Although the exact underlying mechanism is still in debate, what is clear is that steroid administration inhibits protein breakdown, even in the fasted state, which seems clearly indicative of an anti-catabolic effect.