Placental glucose transporter expression is regulated by glucocorticoids
Placental glucose transporter expression is regulated by glucocorticoids
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DOI：
10.1210/jc.84.4.1445
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发表时间：
1999-04-01
影响因子：
5.8
通讯作者：
Desoye, G
中科院分区：
文献类型：
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作者：
Hahn, T;Barth, S;Desoye, G
虽然糖皮质激素在发育和胎儿编程中发挥重要作用，但它们被广泛用于治疗妊娠期间的各种疾病。在各种组织中，糖皮质激素下调葡萄糖转运系统;然而，它们对胎盘中葡萄糖转运蛋白的影响尚不清楚。在本研究中，葡萄糖载体蛋白GLUT 1和GLUT 3定位于人、大鼠和小鼠胎盘的滋养层和内皮细胞。随后，通过北方和蛋白质印迹法研究糖皮质激素是否影响这些分子的信使核糖核酸和蛋白质表达，使用1）在存在或不存在0.5、5和50 μ mol/L曲安西龙的情况下培养的人足月胎盘滋养层细胞; 2）接受单次ip剂量的0.38 mg/kg曲安西龙的大鼠胎盘;和3）携带反义糖皮质激素受体基因构建体的转基因小鼠的胎盘。在所有这些系统中，两种葡萄糖转运蛋白均显著下调（P < 0.05），但转基因小鼠中GLUT 3信使核糖核酸和蛋白水平增加除外。结果表明，曲安西龙是一个有效的调节胎盘GLUT 1和GLUT 3的表达涉及糖皮质激素受体。我们推测，糖皮质激素给药后胎盘葡萄糖转运蛋白的表达受损可能导致不良副作用，其中最重要的是生长迟缓的胎儿，这种治疗在怀孕期间。
Although glucocorticoids play important roles in development and fetal programming, they are widely used for treatment of a variety of diseases during pregnancy. In various tissues, glucocorticoids downregulate glucose transport systems; however, their effects on glucose transporters in the placenta are unknown. In the present study, the glucose carrier proteins GLUT1 and GLUT3 were localized in the trophoblast and endothelium of the human, rat, and mouse placenta. Subsequently, it was investigated whether glucocorticoids affect messenger ribonucleic acid and protein expression of these molecules by Northern and Western blotting using 1) human term placental trophoblast cells cultured in the presence or absence of 0.5, 5, and 50 mu mol/L triamcinolone; 2) placentas of rats that received a single ip dose of 0.38 mg/kg triamcinolone; and 3) placentas of transgenic mice bearing an antisense glucocorticoid receptor gene construct. In all of these systems, both glucose transporters were significantly downregulated (P < 0.05), with the exception of increased GLUT3 messenger ribonucleic acid and protein levels in transgenic mice. The results demonstrate that triamcinolone is a potent regulator of placental GLUT1 and GLUT3 expression involving the glucocorticoid receptor. We speculate that impaired expression of placental glucose transporters after glucocorticoid administration might contribute to the adverse side-effects, the foremost of which is a growth-retarded fetus, of this treatment during pregnancy.