![]() Generalized glucocorticoid resistance is characterized by compensatory increases in circulating pituitary adrenocorticotropic hormone (ACTH) and adrenal cortisol levels in the absence of the clinical signs and symptoms associated with Cushing's syndrome. ![]() Both autosomal recessive and autosomal dominant modes of inheritance have been observed in this form of glucocorticoid resistance. 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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May 2023
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