Everything about Corticosteroid totally explained
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.
Some common natural hormones are
corticosterone (C
21H
30O
4),
cortisone (C
21H
28O
5, 17-hydroxy-11-dehydrocorticosterone) and
aldosterone.
Synthesis
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,
for example 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 (
for example 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.
Further Information
Get more info on 'Corticosteroid'.
|
External Link Exchanges
Do you know how hard it is to get a link from a large encyclopaedia? Well we're different and will prove it. To get a link from us just add the following HTML to your site on a relevant page:
<a href="http://corticosteroid.totallyexplained.com">Corticosteroid Totally Explained</a>
Then simply click through this link from your web page. Our crawlers will verify your link, extract the title of your web page and instantly add a link back to it. If you like you can remove the words Totally Explained and embed the link in article text.
As long as your link remains in place, we'll keep our link to you right here. Please play fair - our crawlers are watching. Your site must be closely related to this one's topic. Any kind of spamming, dubious practises or removing the link will result in your link from us being dropped and, potentially, your whole site being banned. |
