Corticosteroids, cortisol

In addition to the effects of a low insulin/glucagon ratio, long-term changes in metabolism during starvation are induced by the corticosteroid, cortisol. 

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. 

Similar to the anabolic steroids, a large number of synthetic corticosteroids were developed by chemical modifications of the endogenous corticosteroid cortisol (hydrocortisone) (see Fig. 1). Corticosteroids are widely used e.g., for the treat-... 

Imaging/Labeling Applications Alcohols aloesin analytes bile acid A-acetylglucosaminides carnitine enantiomers corticosteroids cortisol cortisone famesyl pyrophosphate (FPP) hydroxy steroids archaeal ether core lipids A-terminal peptide segment of myosin subfragment-1 (S-1) serine-181 thyroid hormones triamcinolone (TMC) ... 

The outer layer or cortex of the adrenal gland is the source of a large group of sub stances known as corticosteroids Like the bile acids they are derived from cholesterol by oxidation with cleavage of a portion of the alkyl substituent on the D ring Cortisol IS the most abundant of the corticosteroids but cortisone is probably the best known Cortisone is commonly prescribed as an antiinflammatory drug especially m the treat ment of rheumatoid arthritis... 

Efforts toward producing synthetic steroids, particularly cortisol, expanded during World War II to enable researchers to explore the possibiUty of medicinal appHcations of corticosteroids. In 1948, the discovery that cortisone dramatically alleviates the symptoms of arthritis led to intensive research on the antiinflammatory properties of corticosteroids. The development of partial and total syntheses for the commercial preparation of cortisone, alternative methods for producing cortisone, and the search for more potent antiinflammatory analogues gready stimulated both academic and industrial steroid research. 

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. 

Corticosteroids are the most efficacious treatment available for the long-term treatment of asthma, and inhaled corticosteroids are considered to be a first-line therapy for asthma (247). In the early 1950s, cortisone (31) and cortisol (29) were used to treat asthma. However, dmgs with fewer side effects and with... 

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). 

Ceruloplasmin (contains Cu + albumin probably more important in physiologic transport of Cu T Corticosteroid-binding globulin (trans-cortin) (binds cortisol)... 

Close monitoring of 24-hour urinary free cortisol levels and serum cortisol levels are essential to identify adrenal insufficiency in patients with Cushing s syndrome. Steroid secretion should be monitored with all drug therapy and corticosteroid replacement given if needed. 

Corticosteroids synthesized by the adrenal gland are mineralocorticoids and GC. Min-eralocorticoids regulate fluid and electrolyte balance by affecting ion transport in the kidney. Cortisol, the primary circulating GC in most species (including humans), has many activities, including resistance to stress, regulation of intermediary metabolism, and immunosuppressive and anti-inflammatory effects. GC synthesis and secretion is... 

Corticosteroids Cortisone Cortisol Dexamethasone Betamethasone Deoxymethasone Prednisone Prednisolone Flumethasone Growth promoter Anti-inflammatory... 

Chronic elevation of corticosteroids has been shown to impair cognitive processes and have neurotoxic effects (Sheline et al. 1996 de Kloet et al. 1999). The cumulative effects of elevated cortisol levels are associated with cognitive impairments in human aging (Lupien et al. 1999). Thus, the cognitive and neuroprotective effects of ginkgo may be partly mediated through its neuroendocrine effects. 

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