As will be discussed in this article, familial generalized glucocorticoid resistance has been associated with different molecular defects of the GR including: point mutations within the ligand-binding domain reduced affinity for glucocorticoid ligands and a decreased intracellular concentration of the receptor protein. This resistance can result in clinical symptoms that are transient and tissue specific, such as steroid-resistant asthma and rheumatoid arthritis, or that are more generalized. Glucocorticoid resistance occurs when glucocorticoids are unable to exert their full effects on specific target tissues. Most, if not all, of these effects are mediated by intracellular glucocorticoid receptors (GRs) that function as ligand-activated transcription factors. Schmidt, in Encyclopedia of Hormones, 2003 I IntroductionĪdrenal glucocorticoid hormones affect the growth, differentiation, and function of a wide variety of target tissues and cell types.
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