JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Studies on steroid receptors in human and rabbit skeletal muscle - clues to the understanding of the mechanism of action of anabolic steroids.

The mechanism of action of steroid hormones in target tissues include the binding of the steroid molecule to specific receptors in the cytoplasm. Steroid receptors may therefore be regarded as mediators of hormone action. The presence of such receptors in tissues reflects their hormone-sensitivity and the receptor levels are indicative of the relative potential for a direct hormonal action on the tissue in question. Using 3H-labeled synthetic ligands and a charcoal adsorption assay, the presence of specific androgen, glucocorticoid and estrogen (in rabbits only) receptors was demonstrated in human and rabbit skeletal muscle cytosol. These tissues can therefore be regarded as targets for these steroids. Scatchard analysis was then used to quantitate the receptors in muscle in different conditions. In back muscle of scoliotic patients, the concentrations of androgen and glucocorticoid receptors were similar on the convex and concave sides, except the concentration of glucocorticoid receptors (per g of wet weight), which was higher on the convex side. The tissue concentration (per g of wet weight) of glucocorticoid and estrogen receptors (but not of androgen receptor) was higher in rabbit soleus (slow-twitch) muscle than in the gastrocnemius/plantaris (fast-twitch) muscle complex. When the concentrations were related to the number of nuclei (i.e. expressed per mg of DNA), however, only the estrogen receptor concentration differed between the muscles (higher in soleus). Muscle atrophy in rabbit gastrocnemius muscle was induced by tenotomy or denervation and led to similar changes with an increase with time in androgen and glucocorticoid receptor levels (expressed per g of wet weight or per mg of protein) and a concomitant loss of muscle weight and protein. The total muscle content of receptors or the receptor concentration expressed per mg of DNA were also increased, but to a lesser extent. Synthetic anabolic-androgenic steroids can act directly on skeletal muscle in view of their capacity to bind to the androgen receptor as shown in the present study. Relative binding affinities of anabolic-androgenic steroids to the androgen receptor were similar in rabbit and rat skeletal muscle and in rat prostate. The protein/DNA ratio in the muscle samples was used as an estimation of the size of the "functional DNA-unit". The results indicate that slow-twitch fibers have smaller "DNA units", but also that muscle atrophy causes a decrease of the size of the "DNA unit".(ABSTRACT TRUNCATED AT 400 WORDS)

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