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The use of in vitro assays based on androgen receptor expression, as described above, can help to assess whether future designer steroids have anabolic’androgenic activity, and can help to minimize in vivo experiments. These approaches can provide useful evidence to government agencies involved in the regulation of drugs to protect public health, test-c 300 mg injectable steroids $45.00 testosterone cypionate. Moreover, the employment of such assays should be of particular benefit to sporting authorities to help stifle legal challenges based on the premise that new designer steroids have unproven anabolic activity and thus should not be subject to doping control and the penalties associated with their administration. It is accepted that the administration of anabolic steroids to healthy women and children has an anabolic effect, and that with the virilizing effects, there is a gain in muscle mass and strength. However, for many years, it was difficult to prove conclusively that the administration of these steroids had a myotrophic effect in healthy young sportsmen, as discussed by Ryan (1976) (see the section ‘Anabolic steroids as performance enhancers in sport’). Around that period, an interesting but speculative biochemical explanation for this difference in response between the sexes was that due to the exposure to testosterone during puberty in men, there is a downregulation of receptors (decrease in responsiveness of receptors often followed by decrease in numbers) in the skeletal muscle and that the androgen receptor population is then saturated with testosterone in the adult, so that no further response can be induced by pharmacological doses of androgens (Wilson, 1988). It was therefore reasoned that any possible myotrophic effect from administration of anabolic steroids to eugonadal men could be via an anticatabolic mechanism rather than a direct anabolic effect. However, the proposed downregulation of androgen receptors in skeletal muscle because of increased androgen exposure was based on a few animal studies at that time (Dahlberg et al. Indeed, Antonio et al. Androgen receptor regulation in different groups of skeletal muscle in response to physiological and supraphysiological exposure to testosterone is intricate, let alone what may occur following administration of xenobiotic anabolic steroids, and the interested reader is referred to the detailed review by Dr F Kadi in the same issue of this journal. Indirect evidence of an antiglucocorticoid effect comes from a case report concerning partial androgen insensitivity syndrome (Tincello et al. A patient with a single amino-acid mutation in the androgen receptor DNA-binding domain (Arg-608 to Lys), which explained his lack of overall response to high-dose androgen treatment at different times in his life, nonetheless, could be induced into a positive nitrogen balance with testosterone administration. An appealing explanation for this finding is that anabolic steroids act as glucocorticoid receptor antagonists. Most binding studies, however, indicate that anabolic steroids have very low binding affinity for the glucocorticoid receptor (Hickson et al. An alternative hypothesis, therefore, is that anabolic steroids may interfere with glucocorticoid receptor expression at the gene level. Over the years, it has become apparent that the endocrinology of skeletal muscle is highly complex, and there is a delicate balance between synthesis and breakdown during growth, health, disease and ageing, as considered by Sheffield-Moore and Urban (2004). It is this complexity that makes it challenging to resolve the significance of anabolic steroids as anticatabolic (and anabolic) agents across the spectrum, from the healthy athlete who desires faster recovery from arduous training schedules where cortisol may be somewhat raised (Hervey, 1982) to the patient with severe physical trauma, such as from a burn injury, where there is extreme hypercortisolaemia and hypoandrogenaemia (Sheffield-Moore and Urban, 2004). The behavioural effects of androgens/anabolic steroids in men and women, including those concerning sexual behaviour, cognitive abilities, aggression and mood, have been reviewed by Lukas (1996), Christiansen (2001, 2004) and Kuhn (2002) and are also discussed in the National Institute on Drug Abuse (NIDA) Research Monographs (Katz and Pope, 1990; Svare, 1990; Yesalis et al. Androgens are critical to the human male sexual behaviour and they can also enhance female sexual desire and arousal. Testosterone appears to play an important role in cognitive functioning, such as attention and alertness, memory and spatial skills, although based on the conclusions of a limited number of studies. With respect to mood, there are significantly positive correlations of endogenous androgen concentrations with a sense of well-being and joyfulness, and negative correlations with depression and anxiety. Major mood syndromes can arise with anabolic steroid use, including mania or hypomania (mania of a mild type) during exposure and depressive symptoms during steroid withdrawal (Pope and Katz, 1994). Anabolic steroid administration is also associated with increased aggression, especially in high-dose users, but this is not a foregone certainty given that the interaction between androgens and behaviour in men and women is complex. It is an entirely reasonable hypothesis that the athlete may learn to recognize and harness the increase in aggression that can arise with steroid use to help drive their training and increase their competitiveness (Brooks, 1978). Furthermore, male athletes who administer anabolic steroids and then withdraw just before competition in anticipation of a drug test may then experience (in the author’s opinion) a lack of motivation and possibly depression, because they will be in a state of androgen deficiency, taking time for testicular steroidogenesis to recover.
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