Saturday, April 10, 2010

Corticosteroids

Corticosteroids are a class of steroid hormones which are secreted by the adrenal cortex. Corticosteroids participate in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.

The corticosteroids are synthesized from cholesterol within the adrenal cortex. Most steroidogenic reactions are catalysed by enzymes of the cytochrome P450 family. They are located within the mitochondria and require adrenodoxin as a cofactor (except 21-hydroxylase and 17a-hydroxylase). Aldosterone and corticosterone share the first part of their biosynthetic pathway. The last part is either mediated by the aldosterone synthase (for aldosterone) or by the 11ß-hydroxylase (for corticosterone). These enzymes are nearly identical (they share 11ß-hydroxylation and 18-hydroxylation functions) but aldosterone synthase is also able to perform an 18-oxidation. Moreover, aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex; 11ß-hydroxylase is found in the zona fasciculata and reticularis.

Corticosteroids are also known as glucocorticoids and mineralocorticoids. They control carbohydrate, fat and protein metabolism. They are also anti-inflammatory by preventing phospholipid release, decreasing eosinophil action and a number of other mechanisms. Mineralocorticoids such as aldosterone control electrolyte and water levels, mainly by promoting sodium retention in the kidney. Some common natural hormones are corticosterone (C21H30O4), cortisone (C21H28O5, 17-hydroxy-11-dehydrocorticosterone) and aldosterone.

Corticosteroids were once thought to be almost miraculous. In 1948, at the Mayo Clinic in Rochester, Minnesota, a group of arthritis patients were given daily injections of a corticosteroid. The results were so striking and the improvement so dramatic that it was thought that the "cure" for arthritis had been discovered. Nevertheless, as the use of corticosteroids expanded over the years, side effects emerged and it was realized that high doses given over prolonged periods of time turned steroids into "scare-oids". Patients were warned of the potential problems, the use of corticosteroids became more conservative, and some patients were so frightened of them they even declined treatment. Corticosteroids are powerful drugs that can have valuable effect if administered within proper guidelines. Understanding how they work and how they can be safely taken is very important. Two of the side effects of using too much corticosteroids are hypertension (high blood pressure) and tumors.

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