The corticosteroids are steroid hormones produced by the adrenal cortex. They consist of 2 major physiologic and pharmacologic groups: (1) glucocorticoids, which have important effects on intermediary 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 adrenocorticosteroid antagonists.
|Addison's disease||Partial or complete loss of adrenocortical function, including loss of glucocorticoid and mineralocorticoid function|
|Adrenal suppression||A suppression of the ability of the adrenal cortex to produce corticosteroids. Most commonly is an iatrogenic effect of prolonged exogenous glucocorticoid treatment|
|Cushing's syndrome||A metabolic disorder caused by excess secretion of adrenocorticoid steroids, which is most commonly due to increased amounts of ACTH|
|Glucocorticoid||A substance, usually a steroid, that activates glucocorticoid receptors (eg, cortisol)|
|Mineralocorticoid||A substance, usually a steroid, that activates mineralocorticoid receptors (eg, aldosterone)|
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 response elements.
Mechanism of glucocorticoid action. This figure models the interaction of a steroid (S; eg, cortisol), with its receptor (R) and the subsequent events in a target cell. The steroid is present in the blood bound to corticosteroid-binding globulin (CBG) but enters the cell as the free molecule. The intracellular receptor is bound to stabilizing proteins, including heat shock protein 90 (Hsp90) and several others (X). When the complex binds a molecule of steroid, the Hsp90 and associated molecules are released. The steroid-receptor complex enters the nucleus as a dimer, binds to the glucocorticoid response element (GRE) on the gene, and regulates gene transcription. The resulting mRNA is edited and exported to the cytoplasm for the production of protein that brings about the final hormone response. (Reproduced, with permission, from Katzung BG, editor: Basic & Clinical Pharmacology, 12th ed. McGraw-Hill, 2012: Fig. 39–4.)
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).
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 ...