TESTOSTERONE
Direct and indirect anabolic effects
Despite the fact that testosterone has been isolated, synthesized, and actively experimented with for many decades, there is still controversy about exactly how steroids affect muscle mass. At the moment, the main way all anabolic/androgenic steroids act anabolically is by directly activating the cellular androgen receptor and increasing protein synthesis. Thus, if we can increase androgen levels from an external source by adding testosterone or a similar anabolic steroid, we can greatly increase the rate of protein retention in the muscle. This is by far the main reason for muscle growth with all anabolic/androgenic steroids. As hormone levels increase, androgen receptors are activated and ultimately the rate of protein synthesis increases.
But muscle growth can be influenced by other indirect mechanisms besides the commonly understood effect of androgens on protein synthesis. An indirect mechanism is one that is not related to androgen receptor activation, but to the effect of androgens on other hormones, or even to the release of locally acting hormones or growth stimulators inside cells (possibly through other membrane-bound receptors). We also have to remember that gaining muscle mass involves not only protein synthesis, but also other factors such as nutrient transport into tissues and protein breakdown. To get the full picture, we need to consider the interaction of androgens with these factors as well. Regarding the first possibility, let us note that studies with testosterone show that this hormone does not increase the transport of amino acids into tissues. This fact probably explains the profound synergy that bodybuilders have noted in recent years when working with insulin, a hormone that strongly increases nutrient transport into muscle cells. But as far as protein breakdown is concerned, we see a second important way in which androgens can influence muscle growth.
Antiglucocorticoid effect of testosterone
Testosterone (and synthetic anabolic/androgenic steroids) can help to increase mass and strength by exerting an anti-catabolic effect on muscle cells. One of the most important indirect mechanisms of action of androgens is thought to be the effect of these hormones on the action of another type of steroid hormone in the body, the glucocorticoids (cortisol is the main representative of this group). Glucocorticoid hormones actually have the exact opposite effect on the muscle cell than androgens do, namely they send an order to release stored protein. This process is called catabolism and is the destruction of muscle tissue. Muscle growth is achieved when the anabolic effects of testosterone are generally more pronounced than the degenerative effects of cortisol. With intense training and proper nutrition, the body tends to accumulate more protein than it excretes, but this basic struggle always remains constant.
However, when taking anabolic steroids, much higher levels of androgens can put glucocorticoids at a disadvantage. As their action is reduced, fewer cells receive the signal to release the protein, and eventually more of it accumulates. It is thought that the main mechanism causing this effect is the displacement by androgens of glucocorticoids bound to the glucocorticoid receptor. In fact, in-vitro studies have confirmed this idea, showing that testosterone has a very high affinity for this receptor. After suggested that some of the anabolic activity is directly mediated by this action. It has also been suggested that androgens may indirectly interfere with DNA binding to the glucocorticoid response element. Although the exact underlying mechanism is still under debate, one thing is clear: Steroid intake suppresses protein breakdown even in a starvation state, clearly indicating an anti-catabolic effect.
Testosterone and creatine
In addition to protein synthesis, increased androgen levels should also promote creatine synthesis in skeletal muscle tissues.Creatine, in the form of creatine phosphate (CP), plays an important role in the production of ATP (adenosine triphosphate), which is the main energy source for muscles. When muscle cells are stimulated to contract, ATP molecules are broken down into ADP (adenosine diphosphate), resulting in the release of energy. The cells then undergo a process using creatine phosphate to quickly restore ADP to its original structure to replenish the ATP concentration. However, during periods of intense activity, this process will not be fast enough to compensate and ATP levels will decrease. This will lead to muscle fatigue and decreased ability to exert strenuous contraction. With increased levels of Creatine Phosphate available to the cells, ATP is replenished at a greater rate, and muscles become stronger and more enduring. This effect explains some of the early strength increase seen with steroid therapy. Although technically not considered anabolic because tissue hypertrophy is not a direct result, the androgenic support of creatine synthesis is certainly still seen as a positive and growth-supporting outcome in the mind of muscle conditioning.
Testosterone and IGF-1
It has also been suggested that there is an indirect mechanism for the effects of testosterone on muscle mass, by insulin-like growth factor. More specifically, studies have noted a clear link between androgens and tissue release of this anabolic hormone. For example, it has been demonstrated that increased IGF-1 receptor concentrations in skeletal muscle are noted when older men receive replacement doses of testosterone. In essence, the cells become ready for IGF-1 action when exposed to testosterone. On the other hand, we see a marked decrease in IGF1 receptor protein levels during androgen deficiency in young men. It turns out that androgens are necessary for the local production and function of IGF-1 in skeletal muscle cells, independent of circulating growth hormone and IGF-1 levels. Since we know for certain that IGF-1 is at least a minor anabolic hormone in muscle tissue, it seems reasonable to conclude that this factor, at least at some level, is involved in the muscle growth noted in steroid therapy.
Direct and indirect steroids?
Considering the supposed indirect effects of testosterone and pondering the efficacy of synthetic anabolic/androgenic steroids. Many are convinced that there are two dichotomous groups or classes of steroids, ignoring the fact that all steroids promote not only muscle growth but also androgenic effects. There is currently no complete separation of these traits, it is clear that they all activate the cellular androgen receptor. Pharmacology experts believe that the theory of direct and indirect steroid classification arose when some noted the low receptor binding affinity of seemingly strong anabolic steroids such as oxymetholone and methandrostenolone. If they don't bind well, yet work well, then something else must be involved. This type of thinking ignores other factors that affect the potency of these compounds, such as their long half-life, estrogenic activity, and weak interaction with restriction binding proteins. Although there may be differences in how different compounds can indirectly stimulate growth, so that one may even find advantages with certain synergistic drug combinations, the primary mode of action of all these compounds is at the androgen receptor. Also, one should not take too seriously the view that steroids X and Y cannot be combined because they compete for the same receptor for growth stimulation, whereas X and Z should be combined because they act through different mechanisms. Such classifications are based on assumptions only, and with reasonable research, different regimens have their place of use and their protocol of use.