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20-September-2008 09:55:48 - Corticosteroid Corticosterone Corticosterone Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved 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. Glucocorticoids such as cortisol control carbohydrate, fat and protein metabolism and are 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. Contents 1 Biosynthesis 2 Uses 3 History 4 References 5 See also Biosynthesis Corticosteroid biosynthetic pathway in rat Corticosteroid biosynthetic pathway in rat 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 17α-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 11β-hydroxylase for corticosterone. These enzymes are nearly identical they share 11β-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; 11β-hydroxylase is found in the zona fasciculata and reticularis. Uses Synthetic drugs with corticosteroid-like effect are used in a variety of conditions, ranging from brain tumors to skin diseases. Dexamethasone and its derivatives are almost pure glucocorticoids, while prednisone and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect. Fludrocortisone Florinef is a synthetic mineralocorticoid. Hydrocortisone cortisol is available for replacement therapy, e.g. in adrenal insufficiency and congenital adrenal hyperplasia. Synthetic glucocorticoids are used in the treatment of joint pain or inflammation arthritis, temporal arteritis, dermatitis, allergic reactions, asthma, hepatitis, systemic lupus erythematosus, inflammatory bowel disease ulcerative colitis and Crohn's disease, sarcoidosis and for glucocorticoid replacement in Addison's disease or other forms of adrenal insufficiency. Topical formulations for treatment of skin, eye diseases uveitis or inflammatory bowel disease are available. Corticosteroids are also used supportively to prevent nausea, often in combination with 5-HT3 antagonists e.g. ondansetron. Typical undesired effects of glucocorticoids present quite uniformly as drug-induced Cushing's syndrome. Typical mineralocorticoid side effects are hypertension abnormally high blood pressure, hypokalemia low potassium levels in the blood, hypernatremia high sodium levels in the blood without causing peripheral edema, metabolic alkalosis and connective tissue weakness Werner, 2005. Clinical and experimental evidence indicates that corticosteroids can cause permanent eye damage by inducing central serous retinopathy CSR, also known as central serous chorioretinopathy, CSC. A variety of steroid medications, from anti-allergy nasal sprays Nasonex, Flonase to topical skin creams, to eye drops Tobradex, to Prednisone have been implicated in the development of CSR. History Tadeusz Reichstein together with Edward Calvin Kendall and Philip Showalter Hench were awarded the Nobel Prize for Physiology and Medicine in 1950 for their work on hormones of the adrenal cortex which culminated in the isolation of cortisone. Corticosteroids have been used as drug treatment for some time. Lewis Sarett of Merck Co. was the first to synthesize cortisone, using a complicated 36-step process that started with deoxycholic acid, which was extracted from ox bile. The low efficiency of converting deoxycholic acid into cortisone led to a cost of US $200 per gram. Russell Marker, at Syntex, discovered a much cheaper and more convenient starting material, diosgenin from wild Mexican yams. His conversion of diosgenin into progesterone by a four-step process now known as Marker degradation was an important step in mass production of all steroidal hormones, including cortisone and chemicals used in hormonal contraception. In 1952, D.H. Peterson and H.C. Murray of Upjohn Co. developed a process that used Rhizopus mold to oxidize progesterone into a compound that was readily converted to cortisone. The ability to cheaply synthesize large quantities of cortisone from the diosgenin in yams resulted in a rapid drop in price to US $6 per gram, falling to $0.46 per gram by 1980. Percy Julian's research also aided progress in the field. The exact nature of cortisone's anti-inflammatory nature remained a mystery for years after however, until the leukocyte adhesion cascade and the role of phospholipase A2 in the production of prostaglandins and leukotrienes was fully understood in the early 1980s. References Werner R 2005. A massage therapist's guide to Pathology. 3rd ion. Lippincott Williams Wilkins, Pennsylvania, USA. See also Cushing's syndrome Vitiligo Steroids general term Fluorometholone List of steroid abbreviations v d e Corticosteroids - glucocorticoid/receptor and mineralocorticoid/receptor A07EA, C05AA, D07, D10AA, H02, R01AD, R03BA, S01BA, S02B, and S03B Endogenous in CAPS Mineralocorticoids ALDOSTERONE, Deoxycorticosterone, Fludrocortisone Glucocorticoids CORTISONE, HYDROCORTISONE/CORTISOL, DESOXYCORTONE, Beclometasone, Betamethasone, Budesonide, Ciclesonide, Cloprednol, Cortivazol, Deflazacort, Dexamethasone, Fluticasone, Flunisolide, Hydrocortisone aceponate, Hydrocortisone buteprate, Hydrocortisone butyrate, Meprednisone, Methylprednisolone, Methylprednisolone aceponate, Mometasone furoate, Paramethasone, Prednicarbate, Prednisolone, Prednisone, Prednylidene, Rimexolone, Triamcinolone Other/ungrouped corticosteroids Alclometasone, Amcinonide, Clobetasol, Clobetasone, Clocortolone, Desonide, Desoximetasone, Diflorasone, Diflucortolone, Difluprednate, Fluclorolone, Fludroxycortide, Flumetasone, Fluocinolone acetonide, Fluocinonide, Fluocortin, Fluocortolone, Fluorometholone, Fluperolone, Fluprednidene, Formocortal, Halcinonide, Halometasone, Loteprednol, Medrysone, Tixocortol, Ulobetasol Aldosterone antagonists Spironolactone, Eplerenone, Potassium canrenoate, Canrenone v d e Major drug groups Gastrointestinal tract/metabolism A stomach acid Antacids, H2 antagonists, Proton pump inhibitors Antiemetics Laxatives Antidiarrhoeals/Antipropulsives Anti-obesity drugs Anti-diabetics Vitamins Dietary minerals Blood and blood forming organs B Antithrombotics Anticoagulants, Antiplatelets, Thrombolytics Antihemorrhagics Cardiovascular system C cardiac therapy/antianginals Cardiac glycosides, Antiarrhythmics, Cardiac stimulant Antihypertensives Diuretics Vasodilators Beta blockers renin-angiotensin system ACE inhibitors, Angiotensin II receptor antagonists, Renin inhibitors Antihyperlipidemics Skin D Emollients Cicatrizant Antipruritics Reproductive system G Hormonal contraception Fertility agents SERMs Sex hormones Endocrine system H Corticosteroids Sex hormones Thyroid hormones Antithyroid agent Infections and infestations J, P Antibiotics Antivirals Vaccines Antifungals Antiparasitic Antiprotozoals, Anthelmintics Malignant and immune disease L Anticancer agents Immunostimulators Immunosuppressants Muscles, bones, and joints M Anabolic steroids Anti-inflammatories NSAID Antirheumatics Corticosteroids Muscle relaxants Brain and nervous system N Anesthetics General, Local Analgesics Anticonvulsants Mood stabilizers Psycholeptic Anxiolytics, Antipsychotics, Hypnotics/Sedatives Psychoanaleptic Antidepressants, Stimulants/Psychostimulants Respiratory system R Bronchodilators Decongestants H1 antagonists Other ATC V Antidotes Contrast media Radiopharmaceuticals Dressing Retrieved from http://en..org/wiki/Corticosteroid Categories: Corticosteroids Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages ÄŒesky Deutsch Español Français Italiano Lietuvių Nederlands 日本語 ‪Norsk bokmÃ¥l‬ Polski Português Română РуÑ?Ñ?кий SlovenÅ¡Ä?ina Suomi This page was last modified on 12 August 2008, at 22:35
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