Endogenous glucocorticoids

Cushing s syndrome a disease caused by the overproduction of endogenous glucocorticoids... 

Orally administered glucocorticoids have substantial adverse effects, including immunosuppression, suppression of the synthesis of endogenous glucocorticoids themselves (that can be a problem when glucocorticoid therapy is stopped), resorption of bone, and retention of water. Nonetheless, they are important drugs for control of inflammation. They also augment resistance to stress. 

The primary endogenic glucocorticoids are hydrocortisone and cortisone. Numerous synthetic analogs of natural glucocorticoids have been made and used, and they have turned out to be more effective, and currently they have almost completely replaced cortisone (prednisolon, prednisone, dexamethasone, and others). 

The observation that mitotane (Lysodren) could produce adrenocortical necrosis in animals led to its use in the palliation of inoperable adrenocortical adenocarcinomas. A reduction in both tumor size and adrenocortical hormone secretion can be achieved in about half of the patients taking the drug. Because normal adrenocortical cells also are affected, endogenous glucocorticoid production should be monitored and replacement therapy administered when appropriate. 

System (3) is a specific method for simultaneously measuring cortisone, hydrocortisone, prednisone, and prednisolone as endogenous glucocorticoids in plasma [151]. A 1 mL sample is extracted with 9 mL of 2 1 dichloromethane-ethyl ether. The extract is washed once with 2 mL of O.IM HCl, twice with 2 mL of O.IM NaOH, and dexamethasone is added as the internal standard. The column is 5 pm silica gel (25 cm x 3.2 mm), and the mobile phase is 1937 20 42 1 dichloromethane-tetrahydrofuran-methanol-anhydrous acetic acid eluted at a flow rate of 1.3 mL/min. Detection is by UV absorbance UV at 254 nm, and a limit of detection of 10 pg/L has been repotted. 

Aminoglutethimide is normally prescribed for patients with breast cancer or Cushings Syndrome. In both cases patients suffer from catastrophic physiological decline. To a profound degree this is notably due to severe over production of endogenous glucocorticoids. The one glucocorticoid most readers would be familiar with is cortisol. 

Grino M, Guillaume V, Boudouresque F, Margioris AN, Grisoli F, Jaquet P, Oliver C, Conte-Devolx B (1988) Characterization of corticotropin-releasing hormone receptors on human pituitary corticotroph adenomas and their correlation with endogenous glucocorticoids. J Clin Endocrinol Metab 67(2) 279-83... 

Depletion of endogenous glucocorticoids in experimental animals can increase the amount of plasma leakage produced by allergen challenge and other inflammatory stimuli (Boschetto et al., 1992 Ohrui et al., 1992). This observation may be important clinically, because the responsiveness of airway blood vessels to inflammatory mediators could increase after glucocorticoid treatment is stopped. 

Chronic intrauterine stress, on the contrary, lowers the risk of RDS by promoting lung maturation, perhaps by increasing endogenous glucocorticoid concentrations. ... 

I Synthetic derivatives of cortisol, the major endogenous glucocorticoid, are used j extensively in the management of inflammatory disorders and for their immuno-... 

A. Tonic Suppression of iNOS Induction by Endogenous Glucocorticoids... 

B. Tolerance to Endotoxin Inhibits the Induction of iNOS Due to Up-Regulation of Endogenous Glucocorticoids... 

Thus, we have investigated the relationship between the early-phase tolerance to endotoxin and the induction of iNOS in vivo. In particular, we have studied (1) whether the early-phase tolerance to endotoxin is associated with a reduced ability of endotoxin to induce iNOS, (2) whether this is associated with increased circulating levels of endogenous glucocorticoids, and (3) whether any rise in plasma glucocorticoids is responsible for suppressing the induction of iNOS and the blunted cardiovascular response to endotoxin in endotoxin-tolerant animals. 

Thus, the development of cardiovascular tolerance to endotoxin in the rat is associated with a reduced ability of endotoxin to induce iNOS, In addition, endotoxin tolerance is associated with a marked rise in plasma glucocorticoid levels. The attenuation of the induction of iNOS by endogenous glucocorticoids is likely to account for endotoxin-induced cardiovascular tolerance. Elevated glucocorticoids play a key role in the development of endotoxin tolerance and may serve to protect individuals with chronic inflammatory disorders from the deleterious consequences of excessive NO production. 

Masferrer, J. L., Seibert, K., Zweifel, B. S., and Needleman, P. (1992b). Endogenous glucocorticoids regulate an inducible cyclooxygenase enzyme. Proc. Natl. Acad. Sci. U.S.A. 89, 3917-3921. 

Szabo, C., Thiemermann, C., and Vane, J. R. (1993b). Endogenous glucocorticoids supress the production of nitric oxide and prostacyclin by bacterial lipopolysaccharide. Proc. R. Soc. B 253, 233-238. 

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