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The corticosteroids are steroid hormones produced by the adrenal cortex. They consist of two major physiologic and pharmacologic groups: (1) glucocorticoids, which have important effects on carbohydrate, fat and protein metabolism, catabolism, immune responses, and inflammation; and (2) mineralocorticoids, which regulate sodium and potassium reabsorption in the collecting tubules of the kidney. This chapter reviews the glucocorticoids, the mineralocorticoids, and the corticosteroid antagonists.
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A. Mechanism of Action
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Corticosteroids enter the cell and bind to cytosolic receptors that transport the steroid into the nucleus. The steroid-receptor complex alters gene expression by binding to glucocorticoid response elements (GREs) or mineralocorticoid-specific elements (Figure 39–1). Tissue-specific responses to steroids are made possible by the presence in each tissue of different protein regulators that control the interaction between the hormone-receptor complex and particular DNA response elements.
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B. Organ and Tissue Effects
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Glucocorticoids stimulate gluconeogenesis. As a result, blood glucose rises, muscle protein is catabolized, and insulin secretion is stimulated. Both lipolysis and lipogenesis are stimulated, with a net increase of fat deposition in certain areas (eg, the face and the shoulders and back).
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Glucocorticoids cause muscle protein catabolism. In addition, lymphoid and connective tissue, fat, and skin undergo wasting under the influence of high concentrations of these steroids. Catabolic effects on bone can lead to osteoporosis. In children, growth is reduced.
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3. Immunosuppressive effects
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Glucocorticoids inhibit cell-mediated immunologic functions, especially those dependent on lymphocytes. These agents are actively lymphotoxic and, as such, are important in the treatment of hematologic cancers. The drugs do not interfere with the development of normal acquired immunity but delay rejection reactions in patients with organ transplants.
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