Hormones, Adrenal‐Cortical
Authors: Avery Mitchell A. , Woolfrey John R. 
Published: July 2004

AbstractAdrenal‐cortical hormones, following the introduction of cortisone and hydrocortisone nearly a half‐century ago, have continued to be the drug of choice in treatment of afflictions ranging from skin rash to severe acute inflammatory disorders and are now included in many other therapeutic regimes. The adrenal cortex releases both mineralocorticoids and glucocorticoids; the latter influence carbohydrate and protein metabolism, and the former regulate sodium reabsorption in the kidney. Moreover, corticosteroids and their metabolites were early noted to possess powerful antiinflammatory and immunomodulatory properties, leading to a massive increase in research in the area of steroid synthesis and physiology, imparting great impetus to the development of synthetic steroids. These exhibited activities far greater than those of the natural hormones, thereby opening the way to development of many more active antiinflammatory agents.Corticosteroids are commonly used as topicals for the suppression of symptoms, including inflammation. Though they are rarely considered curative, many diseases respond well symptomatically to treatment with them, eg, liver disease, acute spinal cord injury, organ transplants, GI diseases, and dermatologic diseases, among others. Mineralocorticoid therapy is less common.Progesterone is the key intermediate in both mineralocorticoid and glucocorticoid biosynthesis. Cortisol and aldosterone are results of oxidations of progesterone. The major metabolic transformations of the adrenal cortical hormones generally follow the metabolism of cortisol. The effects of adrenal‐cortical steroids are thought to result from their interaction with intracellular receptors; these are the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). The primary structure of the GR has been identified as a 795 residue protein; a significant amount of 3‐D structure elucidation of the GR has been made. The process by which adrenocortical steroids impart their action is based on the action of the steroid on a receptor (GR or MR). The use of glucocorticoids leads to antiinflammatory effects by first controlling gene expression, which subsequently leads to the synthesis and/or suppression of inflammation regulatory proteins.Microorganisms are available which transform progesterone and cortisone into steroids. These steroids surpass their parent hormones in antirheumatic and antillergic activity and produce lower levels of side effects. When tested in patients with rheumatoid arthritis, fludrocortisone acetate proved to be 10 times more potent than hydrocortisone acetate. Triamcinolone possesses high glucocorticoid and antiinflammatory activity and is almost entirely devoid of salt‐retaining activity. 2α‐Methyl‐9α‐fluorocortisol has been reported to show enhanced glucocorticoid activity and greatly enhanced mineralocorticoid activity, surpassing aldosterone in sodium‐retaining and potassium‐excreting potency. Hyperaldosteronism is accompanied by elevation of blood pressure and can be treated with an aldosterone antagonist, eg, spironolactone. Antagonists of glucocorticoid and mineralocorticoid activity have found increased use in the treatment of hypertension. The most clinically useful GR antagonist is RU‐486.