Mechanism of Actions

Anabolic steroids are believed to affect athletes by mechanisms that are both physiological and psychological (106). These proposed mechanisms include (1) activating steroid hormone receptors in skeletal muscle cells, (2) producing an anticatabolic effect in the skeletal muscle, and (3) inducing motivational psychological effects. It is presently unclear to what extent each of these mechanisms contributes to the overall physiological adaptation and performance changes found in anabolic steroid users. Most likely, these elements combine synergistically to bring about the changes noted.

Steroid Hormone Receptors

Anabolic steroids activate androgen receptors in skeletal muscle cells, which stimulate the promoters of specific genes and induce protein synthesis (105,106). Of these proteins, one that is important in increased muscle mass and strength is IGF-1 (109). IGF-1 mRNA in skeletal muscle is increased by testosterone treatment in older men (110) and is reduced in testosterone deficiency (111). In certain cells, most notably prostate epithelium, testosterone's action is amplified by its irreversible bioconversion to 5-a dihydrotesterone by the enzyme 5-a-reductase. In skeletal muscle cells, however, the activity of this enzyme is weak (112). The number of muscle androgen receptors is increased by androgens in certain experimental models (113,114). Several transcription factors interact with androgen receptors and upregulate androgen receptor function (115). Of these factors, supervillin, a 205-kDa actin-binding protein, was recently shown to be androgen regulated (116).

Interestingly, exercise training is necessary for anabolic steroids to exert any beneficial effect on performance. As an illustration, research has shown that a greater exercise performance improvement with anabolic steroid use has occurred in experienced weight lifters than in novice subjects (103,105,106). The experienced weight lifters were capable of training with heavier weights and of producing relatively greater muscle tension during exercise. Anabolic steroid effectiveness is also dependent on the number of unbound steroid hormone receptor sites in skeletal muscle, and resistance exercise training (i.e., intensive) may increase the number of unbound receptor sites (43,46,105,106).

Anti-Catabolic Actions

There is evidence that a portion of the anabolic effect of testosterone and anabolic steroids is via an antiglucorticoid action. Cortisol is catabolic, because one of its actions is to induce protein breakdown (25,31,50). Cortisol is secreted in large amounts in response to exercise, which may provide proteins for energy metabolism and deplete the free amino acid pool of proteogenesis precursors (25,31,50). Cortisol receptors are found in skeletal muscle cells, and anabolic steroids bind to these receptors (117,118) to block cortisol from binding. This prevents cortisol from inducing muscle protein breakdown and depleting the free amino acid pool (31,103,106). For example, in men with severe burn injury, testosterone treatment markedly reduced protein breakdown (119). A similar effect could enhance recovery from exercise training by allowing amino acid precursors to be available for tissue repair and regeneration. Interestingly, athletes have indicated that anabolic steroids help them train more intensely and recover faster (103,106).

Psychological Effects

An important aspect of the anabolic steroid effect may be enhancement of the athlete's "motivational psychological state" (106,120). This belief is supported by the notion that athletes indicate their emotional sense of well-being; euphoria, aggressiveness, and tolerance to stress, are all enhanced when they are using these agents. These emotions are positive motivators and allow the athlete to train harder and to perform more intensive exercise training. This, in turn, would allow a greater exercise stimulus to be presented to muscle cells, thus resulting in improved adaptation.

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