Corticosteroids cortisol and

If as above we simply represent alicyclic rings sharing two Gs by a vertical line, then we can represent the basic tetracyclic structure of lanosterol as G61G61 G6 C5 (noting that there are two double bonds and various alkyl substituents and also a 3-hydroxyl on the first of the alicyclic rings). Many subsequent reactions yield cholesterol, a major triterpene membrane component that modifies the fluidity of animal cell membranes and is a precursor for synthesis of animal bile acids (fat solubilizing amphipathic detergents) plant triterpenes and steroid hormones such as the corticosteroids cortisol and cortisone, the mineralocorticoid aldosterone and the sex hormones testosterone and 17-(3-oestradiol. The structure and bioactivity of the plant terpenes is sketched below. 

Adrenocorticotropic hormone derives from the anterior pituitary in response to the leptin-or stress-induced anorexigenic, hypothalamic CRH. Corticotropin (like enkephalins and MSHs) derives from a precursor polypeptide pro-opiomelanocortin. Corticotropin induces the catabolic adrenal cortex corticosteroid cortisol and the mineralocorticoid aldosterone (Chapter 11) and is an important regulator of immune responses including chemotaxis and phagocytosis. Corticotropin acts via GPCRs to activate Gas and increase cAMP in anterior pituitary cells. 

Pregniines. In 1944, Sarrett completed the first partial synthesis of cortisone (172). Like many of the early syntheses of corticosteroids, Sarrett began with the a bile acid, deoxychoHc acid (14). Because bile acids are isolated from animal sources, their supply is by necessity limited (173). Following these early syntheses, several improvements and innovations have resulted in a number of industrial syntheses of cortisol and other corticosteroids. 

Cortisol and Other Corticosteroids Regulate a Variety of Body Processes... 

Interference with corticosteroid function and the stress response has been shown for a variety of chemicals, including the pharmaceutical salicylate (Gravel and Vijayan 2006) and the PAH, phenanthrene (Monteiro et al. 2000a, 2000b). Other classes of chemicals shown to have significant effects on cortisol levels include PCBs and PAHs (Hontela et al. 1992,1997). The precise mechanisms for these effects are poorly understood, but for PCBs, are believed to be via their actions through the Ah receptor (Aluru and Vijayan 2006). 

Kanter et al. reported an increase concentration of the corticosteroid binding globulin (CBG) (Kanter et al. 2001). Most cortisol is bound to CBG, and is biologically inactive. A greater concentration of CBG is consistent with low levels of measurable free cortisol, and provides a putative explanation for how cortisol levels could be measurably low even though other aspects of HPA axis functioning do not seem hypoactive. However, the extent to which CBG levels are a contributing cause of low cortisol requires further examination. 

The adrenal cortex synthesizes corticosteroids (glucocorticoids and mineralocor-ticoids), which differ in activities. In humans, cortisol is the main glucocorticoid, and aldosterone is a main mineralocorticoid. Steroid therapy causes severe potential side effects, hence a careful consideration is always exercised before starting therapy. These are used in variety of disorders such as rheumatic disorder, renal disease, allergic manifestation, bronchial asthma, skin diseases, infectious diseases, malignancy, and hepatic diseases. 

Prednisolone - The stress of surgery causes an increase in plasma adrenocorticotrophic hormone and cortisol concentrations. Cortisol secretion can rise from 30 mg/day to 50 mg/day following minor surgery and 150 mg/day following major surgery. However, an abrupt withdrawal after a prolonged period may lead to acute adrenal insufficiency, hypotension or shock. Thus it is important to continue SC s corticosteroid therapy and additional intravenous hydrocortisone may be administered peri-operatively. 

CORTICOSTEROIDS CALCIUM CHANNEL BLOCKERS 1. Antihypertensive effect of calcium channel blockers are antagonized by corticosteroids 2. t adrenal suppressive effects of corticosteroids, methylprednisolone and prednisolone when co-admin-istered with diltiazem, nifedipine and verapamil. This may t risk of infections and produce an inadequate response to stress scenarios 1. Mineralocorticoids cause sodium and water retention, which antagonizes the hypotensive effects of calcium channel blockers 2. Due to inhibition of metabolism of these corticosteroids 1. Monitor BP at least weekly until stable 2. Monitor cortisol levels and warn patients to report symptoms such as fever and sore throat... 

Intralesional injection of steroid can lead to adrenal suppression. Infents and small children are especially susceptible, because a given amoimt of steroid is distributed in a smaller volume of fluid and tissue compartments. Infents injected with mixtiu es of triamcinolone acetonide and betamethasone or dexamethasone fiar periocular hemangiomas exhibited depressed serum cortisol and adrenocorticotropic hormone levels. The adrenal suppression can last up to 5 months and can result in weight loss and growth retardation. It is not known whether other corticosteroid preparations would produce similar effects or which other fectors might influence these results. In general, topical and periocular use of steroids produces minimal systemic effects. Withdrawal of topical or periocular steroids does not generally cause adrenal crisis. 

Glucocorticoids also have antiallergic properties, as a result of and by an inhibition of the synthesis of histamine by mast cells and basophils. Of the naturally occurring corticosteroids, only cortisol and corticosterone possess glucocorticoid activity, with cortisol the most effective. Cortisone and 11-dehydrocorticosterone lack direct glucocorticoid activity, but have potential glucocorticoid activity because they can be metabolixed to cortisol and corticosterone, respectively. 

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