Glucocorticoids, systemic

Sabatino F, Masoro EJ, McMahan CA, Kuhn RW. Assessment of the role of the glucocorticoid system in aging processes and in the action of food restriction. J Gerontol 1991 46 B171-B179. 

Landfield PW, Cadwallader LB, Vinsant S. Quantitative changes in hippocampal structure following longterm exposure to delta 9-tetrahydrocannabinol possible mediation by glucocorticoid systems. Brain Res 1988 443(l-2) 47-62. 

Corticosteroids 2-i times/day Local tissue atrophy, degeneration, and striae epidermal thinning acneiform eruptions baderial or fungal skin infections glucocorticoid systemic effects... 

Cortisol-Cortisone Conversion. Under normal conditions, this equilibrium slightly favors the oxidized compound. Similarly, the conversion of corticosterone to 11-deoxycorticosterone is also mediated by the liP-hydroxysteroid dehydrogenase enzyme system and requites NAD(P) /NAD(P)H. This conversion is especially important both in the protection of the human fetus from excessive glucocorticoid exposure, and in the protection of distal nephron mineral ocorticoid receptors from glucocorticoid exposure (14). The impairment of this conversion is thought to result in hypertension associated with renal insufficiency (15). 

Because of their considerable side effects - which depend on dose and, even more relevant, on the duration of application - systemically applied glucocorticoids are only used in serious allergic diseases. 

Generally, inhaled glucocorticoids have few side effects, the appearance of which depends on the dose, the frequency of administration, and the delivery system used. The most common side effect is dysphonia (hoarseness), which affects approximately one third of treated patients. Oropharyngeal candidiasis (thrush)... 

Due to the side-effect problems seen with high doses of inhaled glucocorticoids resulting from systemic absorption and the use of oral glucocorticoids in severely affected patients, there has been a search for safer glucocorticoids for inhalation and even for oral administration. As discussed above, a major mechanism... 

Cole et al. (1995) reported on knock-out mice with a germ line deletion of GR. They demonstrated that lack of GR leads to perinatal death, atelectasis of the lung, and lack of adrenalin synthesis. To circumvent perinatal lethality, Tranche et al. (1999) and Brewer et al. (2003) generated tissue-specific somatic deletions of GR. This allowed to characterize GR function in the CNS, the immune system, and the liver in more detail. In particular, these approaches revealed novel aspects of organ-specific glucocorticoid physiology such as anxiety-like behavior, growth control, and polyclonal T cell activation. 

Two main strategies are presently used to suppress immune responses (summarized in Fig. 3). The first focuses on cytokines, the central mediators of the immune system. Efficient inhibition of cytokine production can be achieved by glucocorticoids. Specific anticytokine strategies include the use of monoclonal antibodies, soluble receptors, or receptor constructs. 

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