The mechanism of action of
glucocorticoid hormones on rat skeletal muscle was studied by following their effect on muscle weight, free
amino acid content, activity of
amino acid-metabolizing
enzymes, and binding to
cytoplasmic receptor proteins. A significant reduction of gastrocnemius muscle and
body weight occurred following administration of
cortisol,
triamcinolone diacetate, and
triamcinolone acetonide to adrenalectomized rats. Treatment with
triamcinolone diacetate also reduced the level of several free
amino acids and enhanced the activity of a myofibrillar
protease in skeletal muscle. The
hormone had, however, no effect on the activity of various
enzymes involved in
amino acid catabolism in muscle. In
nephrosis, another condition of muscle wasting, the level of several muscle
amino acids were also reduced to a lesser extent.
Cortisol and
triamcinolone acetonide, both of which induce muscle wasting, were found to bind to two distinct cytoplasmic
proteins in muscle. Binding of the labeled
hormones was followed at 0 C and could be observed in presence of a 1000-fold excess of the catabolically inactive
steroid epicortisol. Binding of 3H-triamcinolone acetonide. In vitro competition experiments further suggest a correlation between
steroid binding to the 3H-dexamethasone or 3H-triamcinolone acetonide site and their potency to induce muscle catabolism. It is concluded that skeletal muscle is a direct target organ for
glucocorticoids, and that muscle responsiveness involves binding of the active
hormones to
cytoplasmic receptor sites.