Cortisone is a pregnane (21-carbon) steroid hormone. It is one of the main hormones released by the adrenal gland in response to stress. In chemical structure, it is a corticosteroid closely related to cortisol. It is used to treat a variety of ailments and can be administered intravenously, orally, intra-articularly (into a joint), or transcutaneously. Cortisone suppresses the immune system, thus reducing inflammation and attendant pain and swelling at the site of the injury. Risks exist, in particular in the long-term use of cortisone.Cortisone, a glucocorticoid, and epinephrine (adrenaline) are the main substances released by the body as a reaction to stress. They elevate blood pressure and prepare the body for a fight or flight response.Oral use of cortisone has a number of potential systemic side-effects: Asthma, hyperglycemia, insulin resistance, diabetes mellitus, osteoporosis, anxiety, depression, amenorrhoea, cataracts, Cushing's syndrome and glaucoma, among other problems.Cortisone was first identified by the American chemists Edward Calvin Kendall and Harold L. Mason while researching at the Mayo Clinic. In 1929, Philip S. Hench and colleagues discovered that cortisone is effective in the treatment of rheumatoid arthritis. Kendall was awarded the 1950 Nobel Prize for Physiology or Medicine along with Philip S. Hench and Tadeus Reichstein for the discovery of adrenal cortex hormones, their structures, and their functions. As it turns out, both Reichstein and the team of O. Wintersteiner and J. Pfiffner had separately isolated the compound prior to Mason and Kendall, but failed to recognize its biological significance. Mason's contributions to the crystallization and characterization of the compound have generally been forgotten outside of the Mayo Clinic.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 (suprarenal) 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 the peripheral tissues, cortisol is converted to cortisone by the enzyme 11-beta-steroid dehydrogenase.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 it as a masterpiece and brilliant indictment of contemporary attitudes towards mental illness and addiction. In 1963, Jean-Luc Godard named it one of the ten best American sound films ever made.John F. Kennedy needed to regularly use corticosteroids such as cortisone as a treatment for Addison's disease.