The glucocorticoid receptor is essential for maintaining basal and dexamethasone-induced repression of the murine corticosteroid-binding globulin gene
The glucocorticoid receptor is essential for maintaining basal and dexamethasone-induced repression of the murine corticosteroid-binding globulin gene
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DOI：
10.1016/s0303-7207(99)00105-7
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发表时间：
1999-08-20
影响因子：
4.1
通讯作者：
Fullerton, MJ
中科院分区：
文献类型：
--
作者：
Cole, TJ;Harris, HJ;Fullerton, MJ
我们研究了缺乏功能性糖皮质激素受体（GR）的小鼠中皮质类固醇结合球蛋白（CBG）基因的肝脏表达和糖皮质激素调节。 GR -/- 小鼠的下丘脑-垂体-肾上腺轴负反馈受损，导致 ACTH 和皮质酮的循环水平升高。这种情况在新生儿期可见，并持续到成年期，此时 ACTH 和皮质酮水平增加至 4-5 倍。尽管皮质酮水平升高，我们发现 GR -/- 小鼠的平均动脉血压没有变化，糖皮质激素代谢酶 11 β-羟基类固醇脱氢酶 1 型 (HSD1) 和 2 型 (HSD2) 的肾活性也没有变化。我们确实发现 CBG 的肝脏表达显着增加，血浆 CBG 水平增加了 50%。在成年 GR -/- 小鼠中检测到 CBG 表达增加，在 18.5 天胚胎 GR -/- 小鼠中，出生时 CBG 肝脏 mRNA 增加超过 10 倍。成年 GR -/- 小鼠也对地塞米松诱导的肝脏 CBG 表达抑制具有抵抗力。这些结果表明，在小鼠中，GR 对于维持肝脏中 CBG 基因表达的基础水平至关重要，并且也是地塞米松诱导的成年 CBG 基因抑制所必需的。 (C) 1999 Elsevier Science Ireland Ltd. 保留所有权利。
We have investigated hepatic expression and glucocorticoid regulation of the corticosteroid-binding globulin (CBG) gene in mice lacking a functional glucocorticoid 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 increased up to 4-5 fold. Despite high elevation of corticosterone we find no change 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 increased hepatic expression of CBG with a 50% increase in plasma CBG levels. Increased 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 embryonic GR -/- mice. Adult GR -/- mice were also resistant to dexamethasone-induced repression of CBG expression in the liver. These results indicate that in mice, GR is essential for maintaining the basal level of CBG gene expression in the liver, and is also required for dexamethasone-induced repression of the CBG gene in the adult. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.