Testosterone fails to prevent skeletal muscle atrophy from glucocorticoids.

This study was undertaken to determine whether testosterone can stimulate muscle growth as well as counteract the muscle wasting caused by excess glucocorticoids. Female rats were divided into four groups: a vehicle (1% carboxymethycellulose)-treated group, a testosterone acetate (Te)-treated group, a cortisol acetate (Co)-treated group, and a Te + Co group. Animals were injected with the steroids (Te, 40 mg/kg body wt; Co, 20 mg/kg body wt) subcutaneously for 12 consecutive days. Absolute gastrocnemius muscle weights were 8% heavier after testosterone treatment, (P less than 0.05), 20% lighter after glucocorticoid treatment, and 18% lighter after both treatments than those of vehicle-treated animals. However, total body weight loss was less in the Te + Co group than in the group receiving just Co. Specific binding of [3H]triamcinolone acetonide, a synthetic glucocorticoid, in femtomoles per milligram gastrocnemius cytosol protein, was similar between the vehicle-treated (52.9 +/- 4.7) and Te-treated (48.9 +/- 3.6) groups. Specific cytosol binding was also depleted to the same extent (to 11-12 fmol/mg protein) by either the Co or Te + Co injections. There was minimal competition by testosterone for glucocorticoid binding; however, most of the displacement was observed in the corticosteroid binder IB form of the activated triamcinolone acetonide-receptor complex on DEAE-cellulose chromatography. We conclude that Te was ineffective in preventing muscle atrophy caused by Co treatment despite its ability to induce muscle growth. The binding specificity studies lead to the conclusion that most of the testosterone and cortisol functioning were occurring primarily through separate receptor systems.