Cortisone
Cortisone is one of several steroid hormones secreted by the cortex (outer covering) of the adrenal gland. These hormones, called corticoids, are classified according to their functions, glucocorticoids controlling sugar metabolism and mineralocorticoids controlling the metabolism of minerals and water. The principal glucocorticoids are corticosterone and hydrocortisone (cortisol) and the principal mineralocorticoid is aldosterone. Cortisone is in both categories, because it quickly converts protein to the carbohydrate glucose and it helps regulate salt metabolism. Cortisone also helps the body withstand stress. It is used medically to reduce inflammation.
The adrenal cortex's production of cortisone is controlled by the hormone ACTH (adrenocorticotropic hormone), which is secreted by the pituitary gland. The pituitary, in turn, responds to corticotropin-releasing factor, a hormone-like substance produced by the portion of the brain called the hypothalamus.
Knowledge of cortisone is due primarily to three scientists, the Swiss chemist Tadeus Reichstein and the Americans Edward Kendall, a biochemist, and Philip Showalter Hench, a medical researcher. Kendall first began work on adrenal cortex hormones because an extract had been used successfully against Addison's disease, which is caused by adrenal gland dysfunction. The original hormone theory, developed by the British physiologists William Bayliss and Ernest Starling, held that each type of gland secreted only one hormone. But by the mid-1930s, Kendall and others believed that the adrenal gland produced many hormones. In 1936 Reichstein was the first to isolate what later was named cortisone. Kendall isolated a series of adrenal substances and converted the one he called Compound E into an active substance. He deduced that it was a steroid.
Hench and Kendall studied Compound E for possible use in treating arthritis. In 1948 and 1949, Hench and Kendall gave the name cortisone to Compound E, and the next year Hench and another colleague were the first to use it to successfully treat arthritis. For their work with cortisone and other adrenal hormones, Reichstein, Hench, and Kendall shared the 1950 Nobel prize in physiology or medicine.
Soon after cortisone's first successful medical use, treatments were discontinued. Researchers found that rheumatoid arthritis is not caused by hormone deficiency, and cortisone treatments have some serious side effects. These included edema (fluid retention), high stomach acidity, damage to bone, and abnormal metabolism of sodium, potassium, and nitrogen. Further experiments, however, yielded a refined product that reduced the side effects.
Cortisone (17-hydroxy-11-dehydrocorticosterone) has been synthesized by several different methods. It was originally derived from the bovine bile constituent deoxycholic acid in a costly 37-step process. A less expensive mass-production method was developed in 1948 by the American chemist Percy Julian, who was widely known for synthesizing chemicals from soybeans. Julian had already synthesized a substance that he called cortexolone, which was very similar to cortisone, except that it had one less oxygen atom. Julian added oxygen to his cortexolone, turning it into cortisone at a greatly reduced production cost.
The American chemist Carl Djerassi (1923-) in 1951 was the first to synthesize cortisone from raw plant materials--yams and sisal (diosgenin and hecogenin). That same year, the American chemist Robert Burns Woodward synthesized cortisone from orthotoluidine, a coal-tar derivative whose structure was one carbon ring with an attached methyl (CH3) group. By adding various groups of atoms, Woodward transformed it into the basic steroid pattern of four rings and two methyl groups. Though twenty steps were involved, Woodward's process was considerably more streamlined than that for converting bovine bile.
Today, cortisone is prescribed to reduce inflammation in allergy and in arthritis and other connective tissue diseases. It is also prescribed as a replacement hormone in Addison's disease, and for people whose adrenal glands have been removed. Other uses include cancer therapy, asthma treatment, and reduction of the body's immune response to prevent rejection of transplanted organs.
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