Interaction of glucocorticoid hormones with rat skeletal muscle: Catabolic effects and hormone binding

doi:10.1016/0026-0495(76)90046-9

Metabolism

Volume 25, Issue 2, February 1976, Pages 157-167

https://doi.org/10.1016/0026-0495(76)90046-9 Get rights and content

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 was competively inhibited by cortisol, but the binding of ³H-cortisol was not affected by triamcinolone acetonide. In vitro competition experiments further suggest a correlation between steroid binding to the ³H-dexa-methasone 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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^☆: Supported by the Bat Sheva de Rothschild Fund for the Advancement of Science and by Public Health Service International Research Fellowship TW-02031 to M. Mayer and NIH Grant CA-05671.

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Interaction of glucocorticoid hormones with rat skeletal muscle: Catabolic effects and hormone binding☆

Abstract

Arch Biochem Biophys

Metabolism

Biochim Biophys Acta

J Biol Chem

J Biol Chem

J Mol Biol

J Biol Chem

J Biol Chem

J Biol Chem

Corticosteroids and accumulation of 14C-labeled amino acids and histamine by isolated rat diaphragm

Am J Physiol

In vitro effects of adrenal steroid hormones on amino acid transport in muscle

Endocrinology

Effects of cortisone on in vitro incorporation of glycine into protein of rat diaphragm

Endocrinology

Corticosteroids and accumulation of ¹⁴C-labeled amino acids and histamine by isolated rat diaphragm