Korn S H, Koerts-de Lang E, Engel G E, Arends J W, Wouters E F, Thunnissen F B
Department of Pulmonology, Maastricht University, The Netherlands.
J Muscle Res Cell Motil. 1998 Oct;19(7):757-65. doi: 10.1023/a:1005439118259.
The aim of the present study was to investigate the occurrence and autoregulation of both glucocorticoid receptor mRNAs in rat gastrocnemius muscle. The expression of both receptor forms was studied 1, 4 or 12 hours after intra-tracheal instillation of a high dose (100 micrograms) of budesonide; muscular expression was compared with glucocorticoid receptor expression in lung tissue. After Northern blot analysis, hybridization was performed with glucocorticoid receptor, glyceraldehyde-3-phosphate dehydrogenase and glutamine synthetase probes. In the gastrocnemius muscle, both the alpha and beta glucocorticoid receptor mRNA forms were detected and found to be downregulated four hours after the budesonide instillation. alpha/beta glucocorticoid receptor ratios were lower in the gastrocnemius (1.1 +/- 0.2) than in the lungs (2.6 +/- 0.6). In the lungs, at all time points, the average alpha glucocorticoid receptor mRNA levels did not differ from controls, although glutamine synthetase mRNA levels were upregulated. The beta glucocorticoid receptor mRNA was slightly reduced at 1 and 4 hours. In conclusion, after intra-tracheal instillation of budesonide, both alpha and beta glucocorticoid receptor forms were downregulated in muscle tissue. The difference in alpha/beta glucocorticoid receptor mRNA ratios and concentrations between lung and gastrocnemius muscle supports the hypothesis of differential gene regulation by glucocorticoids in different cell types.
本研究的目的是调查大鼠腓肠肌中糖皮质激素受体两种mRNA的发生情况及自身调节。在气管内滴注高剂量(100微克)布地奈德后1、4或12小时,研究了两种受体形式的表达;将肌肉表达与肺组织中的糖皮质激素受体表达进行比较。经过Northern印迹分析后,用糖皮质激素受体、甘油醛-3-磷酸脱氢酶和谷氨酰胺合成酶探针进行杂交。在腓肠肌中,检测到α和β两种糖皮质激素受体mRNA形式,并且发现布地奈德滴注后4小时它们被下调。腓肠肌中的α/β糖皮质激素受体比率(1.1±0.2)低于肺中的比率(2.6±0.6)。在肺中,在所有时间点,尽管谷氨酰胺合成酶mRNA水平上调,但α糖皮质激素受体mRNA平均水平与对照组无差异。β糖皮质激素受体mRNA在1小时和4小时时略有降低。总之,气管内滴注布地奈德后,肌肉组织中的α和β两种糖皮质激素受体形式均被下调。肺和腓肠肌中α/β糖皮质激素受体mRNA比率和浓度的差异支持了糖皮质激素在不同细胞类型中进行差异基因调节的假说。