Actions of Glucocorticoids

Glucocorticoids affect various cells in a manner that is characteristic of steroid hormones (see Chapter 28, Fig. 28-3). In general, steroids alter protein synthesis in responsive cells through a direct effect on the cell s nucleus. These hormones alter the transcription of specific DNA genes, which results in subsequent changes in RNA synthesis and the translation of RNA into cellular proteins.6,73 

Specifically, glucocorticoids exert their classic cellular effects first by entering the target cell and binding to a receptor located in the cytosol.19,33 Binding the glucocorticoid to the receptor creates an activated hormone-receptor complex. This activated complex then travels (translocates) to the nucleus of 

FIGURE 29-3 Circadian rhythm of cortisol production in humans. Peak plasma cortisol levels normally occur approximately at the time an individual awakens (6 to 8 am). (Adapted from Katzung BG. Basic and Clinical Pharmacology. 2nd ed. Lange Medical Publications New York 1984 454 after Liddle, 1966. Reproduced with permission of the McGraw-Hill Companies.) 

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Glucocorticoids are powerful anti-inflammatory agents. Which of the following is rwt an anti-inflammatory mechanism of action of glucocorticoids ... 

Galon, J. et al., Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells, FASEB J., 16, 61, 2002. 

Barnes, P.J., Anti-inflammatory actions of glucocorticoids Molecular mechanisms, Clin. Sci. (Colch.), 94, 557, 1998. 

Hormonal drags do not cure cancer, although they do exhibit pronounced palliative action, with the exception of the cytotoxic action of glucocorticoids on lymphoid cells. In particular, this concerns predinsone, which is used to treat lymphomas and certain leukemias in combination therapy. 

Immunodepressive action of glucocorticoids is connected with a decreased level of lymphocytes, eosinophiles, and basophiles in the blood, suppression of antigen recognition, and with suppression of the phase of lymphocyte prohferation. 

Carbohydrate action of glucocorticoids is defined as the stimulation of glucose formation, diminution of its use, and promotion of its storage as glycogen. 

Possible site or sites of action of glucocorticoids on prostanoid production. 

Anabolic activities of testosterone, such as increases in amino acid incorporation into protein and in RNA polymerase activity, have been demonstrated in skeletal muscle. Apart from the direct anabolic effects in specific tissue, androgens antagonize the protein catabolic action of glucocorticoids. The androgen compounds with the greatest ratio of protein anabolic effects to virilizing effects are the 19-nortestosterone derivatives. Compounds that are used clinically (Table 63.3) include nandrolone phenpropionate (Durabolin), nandrolone decanoate... 

Yu S, Holsboer F, Almeida OF Neuronal actions of glucocorticoids Focus on depression. J Steroid Biochem Mol Biol 2008 108(3-5) 300. 

Rhen T, Cidlowski JA. 2005. Antiinflammatory action of glucocorticoids - new mechanisms for old drugs. NEJM. 353 1711-1723. 

Barnes PJ. Anti-inflammatory actions of glucocorticoids molecular mechanisms. Clin Sci. 1998 94 557-572. 

Franchimont D. Overview of the actions of glucocorticoids on the immune response a good model to characterize new pathways of immunosuppression for new treatment strategies. Ann NY Acad Sci. 2004 1024 124-137. 

Hall, E.D., Riker, W.F. and Baker, T. (1983) Beneficial action of glucocorticoid treatment on neuromuscular transmission during early motor nerve degeneration, Exp. Neurol. 79, 488—496. 

Borski, R.J. Nongenomic membrane actions of glucocorticoids in vertebrates. Trends Endocrinol. Metab. 11 427-436, 2000. 

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