The Role of 5a Reduction of Testosterone in the Muscle

Although the enzyme 5-a-reductase is expressed at low concentrations in muscle (90), it is unknown whether conversion of testosterone to DHT is required for mediating the androgen effects on the muscle. Men with benign prostatic hypertrophy who are treated with the a 5-a reductase inhibitor do not experience muscle loss. Similarly, individuals with congenital 5-a-reductase deficiency have normal muscle development at puberty. These data imply that 5-a reduction of testosterone is not obligatory for mediating its anabolic effects on the muscle cells. Because testosterone effects on the prostate involve conversion to DHT, selective androgen receptor modulators that bind the androgen receptor but are not 5-a reduced would be attractive (91). Such agents could produce desirable anabolic effects on muscle without the undesirable effects on the prostate.

Sattler et al. (92) reported that serum DHT levels are lower and the ratio of testosterone to DHT levels is higher in HIV-infected men than in healthy men. From these data, the investigators proposed that an abnormality in the conversion of testosterone to DHT may contribute to wasting in a subset of HIV-infected men. If this hypothesis were true, then it would be rational to treat HIV-AIDS patients with DHT rather than with testosterone. A DHT gel is currently under clinical investigation. However, unlike testosterone, DHT is not aromatized to estradiol. Therefore, there is concern that suppression of endogenous testosterone and estradiol production by DHT may produce osteoporosis and other undesirable adverse effects.

The Bible of Body Building

The Bible of Body Building

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