The glucocorticoid receptor is essential for maintaining basal and dexamethasone-induced repression of the murine corticosteroid-binding globulin gene

We have investigated hepatic expression and glucocorticoid regulation of th e corticosteroid-binding globulin (CBG) gene in mice lacking a functional g lucocorticoid receptor (GR). GR -/- mice show impaired negative feedback in the hypothalamic-pituitary-adrenal axis, resulting in elevated circulating levels of ACTH and corticosterone. This is seen in the neonatal period and continues into adulthood where ACTH and corticosterone levels are increase d up to 4-5 fold. Despite high elevation of corticosterone we find no chang e in mean arterial blood pressure in GR -/- mice and no change in the renal activity of the glucocorticoid-metabolising enzymes 11 beta-hydroxysteroid dehydrogenase type-1 (HSD1) and type-2 (HSD2). We do find markedly increas ed hepatic expression of CBG with a 50% increase in plasma CBG levels. Incr eased expression of CBG was detected in adult GR -/- mice and also at birth with a greater than 10-fold increase in CBG hepatic mRNA in day-18.5 embry onic GR -/- mice. Adult GR -/- mice were also resistant to dexamethasone-in duced repression of CBG expression in the liver. These results indicate tha t in mice, GR is essential for maintaining the basal level of CBG gene expr ession in the liver, and is also required for dexamethasone-induced repress ion of the CBG gene in the adult. (C) 1999 Elsevier Science Ireland Ltd. Al l rights reserved.