Кортизон: Кортизолдың алды және метаболиті

Corticosteroid precursor and metabolite of cortisol

Cortisone is a pregnene (21 carbon) steroid hormone. It is a naturally occurring corticosteroid metabolite that is also used as a pharmaceutical prodrug. Cortisol is converted by the action of the enzyme corticosteroid 11 beta dehydrogenase isozyme 2 into the inactive metabolite cortisone, particularly in the kidneys. This is done by oxidizing the alcohol group at carbon 11 (in the six membered ring fused to the five membered ring). Cortisone is converted back to the active steroid cortisol by stereospecific hydrogenation at carbon 11 by the enzyme 11β Hydroxysteroid dehydrogenase type 1, particularly in the liver. The term "cortisone" is frequently misused to mean either any corticosteroid or hydrocortisone, which is in fact cortisol. Many who speak of receiving a "cortisone shot" or taking "cortisone" are more likely receiving hydrocortisone or one of many other, much more potent synthetic corticosteroids. Cortisone can be administered as a prodrug, meaning it has to be converted by the body (specifically the liver, converting it into cortisol) after administration to be effective. It is used to treat a variety of ailments and can be administered intravenously, orally, intra articularly (into a joint), or transcutaneously. Cortisone suppresses various elements of the immune system, thus reducing inflammation and attendant pain and swelling. Risks exist, in particular in the long term use of cortisone. However, using cortisone only results in very mild activity, and very often more potent steroids are used instead.

Oral use of cortisone has a number of potential systemic adverse effects, including asthma, hyperglycemia, insulin resistance, diabetes mellitus, osteoporosis, anxiety, depression, amenorrhoea, cataracts, glaucoma, Cushing's syndrome, increased risk of infections, and impaired growth.

Cortisone was first identified by the American chemists Edward Calvin Kendall and Harold L. Mason while researching at the Mayo Clinic. During the discovery process, cortisone was known as compound E (while cortisol was known as compound F). In 1949, Philip S. Hench and colleagues discovered that large doses of injected cortisone were effective in the treatment of patients with severe rheumatoid arthritis. Kendall was awarded the 1950 Nobel Prize for Physiology or Medicine along with Philip Showalter Hench and Tadeusz Reichstein for the discovery of the structure and function of adrenal cortex hormones including cortisone. Both Reichstein and the team of O. Wintersteiner and J. Pfiffner had separately isolated the compound prior to the discovery made by Mason and Kendall, but failed to recognize its biological significance. On September 30, 1949, Percy Julian announced an improvement in the process of producing cortisone from bile acids. This eliminated the need to use osmium tetroxide, a rare, expensive, and dangerous chemical. In the UK in the early 1950s, John Cornforth and Kenneth Callow at the National Institute for Medical Research collaborated with Glaxo to produce cortisone from hecogenin from sisal plants.

Cortisone is one of several end products of a process called steroidogenesis. This process starts with the synthesis of cholesterol, which then proceeds through a series of modifications in the adrenal gland to become any one of many steroid hormones. One end product of this pathway is cortisol. For cortisol to be released from the adrenal gland, a cascade of signaling occurs. Corticotropin releasing hormone released from the hypothalamus stimulates corticotrophs in the anterior pituitary to release ACTH, which relays the signal to the adrenal cortex. Here, the zona fasciculata and zona reticularis, in response to ACTH, secrete glucocorticoids, in particular cortisol. In various peripheral tissues, notably the kidneys, cortisol is inactivated to cortisone by the enzyme corticosteroid 11 beta dehydrogenase isozyme 2. This is crucial because cortisol is a potent mineralocorticoid and would cause havoc with electrolyte levels (raising blood sodium and lowering blood potassium levels) and raise blood pressure if it were not inactivated in the kidneys.

Addiction to cortisone was the subject of the 1956 motion picture Bigger Than Life, produced by and starring James Mason. Though it was a box office flop upon its initial release, many modern critics hail the film as a masterpiece and brilliant indictment of contemporary attitudes toward mental illness and addiction. In 1963, Jean Luc Godard named it one of the ten greatest American sound films ever made. John F. Kennedy was regularly administered corticosteroids such as cortisone as a treatment for Addison's disease.