Mechanisms of disease: regulation of glucocorticoid and receptor levels--impact on the metabolic syndrome.
Glucocorticoids exert their effects in target tissues predominantly through their interaction with the glucocorticoid receptor, a member of the nuclear receptor superfamily of transcription factors. Over the years many studies have linked hormone responsiveness, both in vitro and in vivo, to the levels of both glucocorticoid and glucocorticoid receptor; furthermore, an impact of glucocorticoid receptor subcellular trafficking on hormone response has been revealed. This review will focus on the molecular mechanisms responsible for the regulation of glucocorticoid receptor trafficking and expression, and will highlight work that revealed selective physiological effects of altered glucocorticoid receptor expression. The role of alterations in glucocorticoid levels and glucocorticoid receptor function in the metabolic syndrome will also be discussed.
Witchel
Selma F
SF
Division of Pediatric Endocrinology, Children's Hospital of Pittsburgh, and University of Pittsburgh School of Medicine, Pittsburg, PA 15261, USA.
DeFranco
Donald B
DB
D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D000818:Animals; D047109:Fetal Development; D018507:Gene Expression Regulation, Developmental; D005938:Glucocorticoids / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000209:etiology; D008099:Liver / Q000378:metabolism; D024821:Metabolic Syndrome / Q000209:etiology*; D008954:Models, Biological; D009132:Muscles / Q000378:metabolism; D009765:Obesity / Q000209:etiology; D009928:Organ Specificity; D010179:Pancreas / Q000378:metabolism; D011110:Polymorphism, Genetic; D011489:Protein Denaturation; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
D005938:Glucocorticoids; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; D042842:11-beta-Hydroxysteroid Dehydrogenases