Kruskemper (1968) discusses the many failings of the procedures used for determining the myotrophic’androgenic index, for example, the seminal vesicles react more slowly to certain androgens, so that with short test administration, distortions can arise in favour of the myotrophic effect. The harshest criticism of this index was given by Nimni and Geiger (1957), Scow and Hagan (1957) and Hayes (1965). Testosterone administration for 56 days to young gonadectomized rats (castrated at 20’23 days of age) had no effect on the growth of the thigh muscle compared with controls, yet there was considerable growth in the perineal musculature (Scow, 1952; Scow and Hagan, 1957). Testosterone propionate or norethandrolone (17?-ethyl-19-nortestosterone; also an anabolic steroid) administration promoted the growth of the levator ani muscle even in young normal or castrated rats on a protein-free diet, that is, a local anabolic effect proceeding at the expense of catabolic processes in other organs. Hayes (1965) stated that the rat levator ani muscle is not homologous to this muscle in other species, that is, it is not a typical sphincter muscle and does not lift the anus in rodents but is part of the male reproductive system. Thus, Hayes renamed the levator ani muscle, calling it the dorsal bulbocavernosus. All three groups of workers showed that the levator ani muscle reflects a general genitomyotrophic response rather than an overall response to androgens. Later, Hervey (1982) claimed that the male rat’s characteristics are determined shortly after birth (due to a brief secretion of testosterone), and, thereafter, any increase in body mass is not affected by androgens. Contrary to the opinions described above, there is nonetheless biochemical evidence that suggests that the genitomyotrophic response of the levator ani muscle may serve as an indicator of the general myotrophic responses in the developing rat for the following reasons. The same classic androgen receptor can be characterized in the prostate, the bulbocavernosus/levator ani muscle and typical skeletal muscles of the rat (Krieg and Voigt, 1977). Nandrolone (19-nortestosterone) and 5?-DHT have a higher binding affinity than testosterone with the receptor. The prostate has 7 times the concentration of androgen receptors than the bulbocavernosus/levator ani muscles which in turn has 10 times more than other skeletal muscle. In vitro studies by Gloyna and Wilson (1969) and Massa and Martini (1974) have shown that 5?-reductase activity is very high in rat sexual tissue such as the prostate and seminal vesicles but negligible, if at all, in skeletal muscle such as the levator ani and thigh muscle. Intracellular DHT is, therefore, low in skeletal muscle, and it is worth emphasizing that its presence is further diminished because of the high activity of the enzyme 3?-hydroxysteroid-dehydrogenase in this tissue (and cardiac tissue as well), the enzyme that converts DHT irreversibly to 3?-androstanediol (Massa and Martini, 1974; Smith et al. The very low activity of 5?-reductase in skeletal (and cardiac) muscle was subsequently confirmed by other investigators (Krieg et al. The rat levator ani may be a somewhat atypical striated muscle because of its greater concentration of androgen receptors, but, due to its very low 5?-reductase activity, it can also be argued that it is not a typical part of target tissues associated with the reproductive system. Celotti and Cesi (1992), in their review of possible mechanisms of action of anabolic steroids, discuss that the peculiar androgen sensitivity of this muscle is intermediate between that present in the skeletal muscles and that of the prostate. The myotrophic effect of anabolic steroids may be reflected by the amplified response of the levator ani muscle due to its higher concentration of androgen receptors, an effect that is not apparently sufficient in other (typical) rat skeletal muscles to be observed using differences in weight (compared with controls) as the measurand. A possible basis for increasing the myotrophic-to-androgenic ratio may be by exploiting the fundamental difference between the 5?-reductase concentrations in skeletal muscle and androgenic tissue. One way of increasing the anabolic’androgenic dissociation is to administer a steroid that has a greater binding affinity for the androgen receptor but upon reduction to a 5-metabolite has a lesser affinity., anabolic steroids legal usa. Among the anabolic steroids, 19-nortestosterone (nandrolone) was one of the first synthesized, the most used and probably the best studied. Although DHT has a greater binding affinity for the androgen receptor than its parent steroid testosterone, by contrast the 5?-reduced form of 19-nortestosterone, 5?-dihydro-19-nortestosterone, has a lesser binding affinity than its parent steroid 19-nortestosterone (Toth and Zakar, 1982). Hence, in androgenic tissue, testosterone is converted to a more potent metabolite, whereas 19-nortestosterone is converted to a less potent one. As 5?-reduction occurs readily in androgenic tissue but is negligible in skeletal muscle, this explains why 19-nortestosterone has a greater myotrophic-to-androgenic ratio when compared with testosterone ( Figure 6 ). If the model is correct, such a diminishment in androgenic activity should not be confined to the accessory reproductive tissues in the human such as the prostate, but also in non-genital target tissues where clear roles for the metabolism to DHT have been defined such as the male patterns of facial and body hair growth, thus allowing more muscle per whisker.
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