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大鼠海马神经元内11#beta#-HSD1和GR的共存及其意义

万顺伦, 廖茂瑶, 郝如松, 李召峰, 孙刚

第二军医大学生理学教研室.上海 200433

摘要

研究旨在探讨糖皮质激素代谢酶--11#beta#-羟基类固醇脱氢酶Ⅰ型(11#beta#-HSD1)和糖皮质激素受体(GR)在大鼠海马神经元内的共同分布及其意义。用免疫细胞化学方法研究显示,海马神经元内不仅存在11#beta#-HSD1免疫反应物质,还存在GR免疫反应物质,而且11#beta#-HSD1与GR共存于同一海马神经元内。用Western印迹杂交和薄层层析(TLC)方法研究表明,地塞米松(DEX)可以促进11#beta#-HSD1蛋白表达及其酶的活性。利用11#beta#-HSD1基因启动子区序列构建的以CAT酶为报告基因的pBLCAT6质粒转染PC12细胞,证实DEX能够促进CAT酶的表达。以上糖皮质激素的作用均可为GR受体阻断剂RU38486所阻断。结果提示:糖皮质激素(GC)与GR结合后,可以作用于与其共存的11#beta#-HSD1基因启动子区,使11#beta#-HSD1表达增加,从而使更多的GC代谢产物转化为有活性的GC。此机制可能与保证GC在海马神经元与亲和力较低的GR结合有关。

关键词： 11β-羟基类固醇脱氢酶Ⅰ型; 糖皮质激素受体; 海马神经元

Colocalization of 11#beta#-hydroxysteroid dehydrogenase type I and glucocorticoid receptor and its significance in rat hippocampus

Wan Shunlun, Liao Maoyao, Hao Rusong, Li Zhaofeng, Sun Gang

Department of Physiology,The Second Military Medical University.Shanghai 200433

Abstract

This paper was designed to observe the colocalization of 11#beta#-HSD1 and GR, and its significance in the rat hippocampus. Immunocytochemical dual-staining showed that not only 11#beta#-HSD1 but also GR immunoreactive substances were present in the cultured rat hippocampal neurons. Moreover, they were colocalized in the same hippocampal neuron. Synthetic glucocorticoid dexamethasone (DEX) up-regulated the protein expression and activity of 11#beta#-HSD1 in the cultured hippocampal neurons, as determined by Western blot and thin layer chromatography (TLC) respectively. The transfection of PC12 cells with the plasmid containing promoter sequence of 11#betA#-HSD1 gene and the reporter gene of CAT enzyme was conducted. DEX up-regulated the reporter gene expression in the system described above. The up-regulation of 11#beta#-HSD1 and reproter gene expression induced by DEX were both blocked by GR antagonist RU38486. Our study suggests that the colocalization of 11#beta#-HSD1 and GR in the hippocampus may be implicated in the up-regulation of 11#beta#-HSD1 expression by glucocorticoids combining to its promoter region, which in turn produces more biologically active glucocorticoids necessary for the binding of low affinity of GR.

Key words: 11#beta#-hydroxysteroid dehydrogenase type I;Glucocorticoid receptor;Hippocampus

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引用本文：

万顺伦, 廖茂瑶, 郝如松, 李召峰, 孙刚. 大鼠海马神经元内11#beta#-HSD1和GR的共存及其意义[J]. 生理学报 2002; 54 (6): .

Wan Shunlun, Liao Maoyao, Hao Rusong, Li Zhaofeng, Sun Gang. Colocalization of 11#beta#-hydroxysteroid dehydrogenase type I and glucocorticoid receptor and its significance in rat hippocampus. Acta Physiol Sin 2002; 54 (6): (in Chinese with English abstract).