Ratineau C, Roche C, Chuzel F, Cordier-Bussai M, Blanc M, Bernard C, Cuber J C, Chayvialle J A
INSFRM U45, Hôpital Edouard Herriot, Lyon, France.
J Endocrinol. 1996 Oct;151(1):137-45. doi: 10.1677/joe.0.1510137.
The effect of glucocorticoids on the expression of intestinal cholecystokinin (CCK) was investigated both in vivo and in cell culture systems. In vivo, 2-day administration of methylprednisolone to adult male rats induced a decrease in CCK-like immunoreactivity (CCK-L1) and CCK mRNA levels in mucosal extracts. In two CCK-producing cell lines, RIN 1056E and STC-1 of pancreatic and intestinal origin respectively, dexamethasone induced dose-dependent decreases in both CCK-L1 and steady-state CCK mRNA levels. The decrease in CCK mRNA was totally prevented by incubation of cells with an excess of RU 38486, a competitive inhibitor for the binding of glucocorticoids to their receptor. Actinomycin D, used to prevent RNA synthesis, did not modify CCK mRNA stability in dexamethasone-pretreated cells as compared with cells not exposed to dexamethasone. When cells were first incubated with actinomycin D, subsequent addition of dexamethasone left the steady-state CCK mRNA levels unaltered in both cell lines. Nuclear run-on assays performed in RIN 1056E cells showed that glucocorticoids decreased the rate of transcription of the CCK gene. In addition, cycloheximide, used to prevent protein synthesis, abolished the inhibitory effects of dexamethasone on steady-state CCK mRNA levels. These results demonstrate that glucocorticoids down-regulate CCK gene expression in the rat intestinal mucosa and in two CCK-producing cell lines. The effect is blocked by a glucocorticoid receptor antagonist. Inhibition of CCK gene expression may result from a decrease in the transcription rate, and probably involves one or several steps that depend on protein synthesis.
在体内和细胞培养系统中研究了糖皮质激素对肠道胆囊收缩素（CCK）表达的影响。在体内，对成年雄性大鼠连续2天给予甲泼尼龙可导致黏膜提取物中CCK样免疫反应性（CCK-L1）和CCK mRNA水平降低。在两种分别源自胰腺和肠道的CCK产生细胞系RIN 1056E和STC-1中，地塞米松可诱导CCK-L1和稳态CCK mRNA水平呈剂量依赖性降低。用过量的RU 38486（一种糖皮质激素与其受体结合的竞争性抑制剂）孵育细胞可完全阻止CCK mRNA的降低。与未暴露于地塞米松的细胞相比，用于阻止RNA合成的放线菌素D并未改变地塞米松预处理细胞中CCK mRNA的稳定性。当细胞先用放线菌素D孵育，随后添加地塞米松时，两种细胞系中的稳态CCK mRNA水平均未改变。在RIN 1056E细胞中进行的核转录分析表明，糖皮质激素降低了CCK基因的转录速率。此外，用于阻止蛋白质合成的环己酰亚胺消除了地塞米松对稳态CCK mRNA水平的抑制作用。这些结果表明，糖皮质激素下调大鼠肠黏膜和两种CCK产生细胞系中CCK基因的表达。该作用被糖皮质激素受体拮抗剂阻断。CCK基因表达的抑制可能是由于转录速率降低所致，并且可能涉及一个或几个依赖于蛋白质合成的步骤。
