Interaction of glucocorticoid hormones with rat skeletal muscle: catabolic effects and hormone binding. |
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Authors: | M Mayer E Shafrir N Kaiser R J Milholland F Rosen |
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Institution: | 1. Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel;2. the Department of Experimental Therapeutics, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, N.Y. USA;3. Grace Cancer Drug Center, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, N.Y. USA |
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Abstract: | 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. |
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Keywords: | Dexamethasone 9α-fluoro-11β 17α 21-trihydroxy 16α-methyl-pregna-1 4-diene-3 20-dione Triamcinolone 9α-fluoro-11β 16α 17α 21-tetrahydroxypregna-1 4-diene-3 20-dione Epicortisol 11α 17α 21-trihydroxypregna-4-ene-3 20-dione Cortexolone 11-deoxycortisol pregn-4-ene-17α 21-diol-3 20-dione |
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