Primary Generalized Glucocorticoid Resistance and Hypersensitivity: The End-Organ Involvement in the Stress Response

被引:15
作者
Charmandari, Evangelia [1 ,2 ]
机构
[1] Univ Athens, Sch Med, Aghia Sophia Childrens Hosp, Div Endocrinol Metab & Diabet,Dept Pediat 1, GR-10679 Athens, Greece
[2] Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Endocrinol & Metab, Athens 11527, Greece
关键词
LIGAND-BINDING DOMAIN; RECEPTOR GENE; POINT MUTATION; CLINICAL-IMPLICATIONS; ASSOCIATION; POLYMORPHISM; MECHANISMS; OBESITY; EXPRESSION; DISEASE;
D O I
10.1126/scisignal.2003337
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Primary generalized glucocorticoid resistance (PGGR or Chrousos syndrome) and primary generalized glucocorticoid hypersensitivity (PGGH) are rare genetic disorders characterized by generalized, partial target-tissue insensitivity or hypersensitivity to glucocorticoids, respectively, while also causing compensatory alterations in the activity of the hypothalamic-pituitary-adrenal axis. The molecular basis of Chrousos syndrome and PGGH has been ascribed to mutations in the gene encoding the human glucocorticoid receptor (hGR), which impair glucocorticoid signal transduction and alter tissue sensitivity to glucocorticoids. Alterations in hGR action may have important implications for many critical biological processes, such as the behavioral and physiologic responses to stress, immune responses, growth, and reproduction. This Presentation summarizes the pathophysiology, clinical manifestations, and molecular mechanisms of the PGGR and PGGH states.
引用
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页数:6
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