Sheppard K E, Li K X, Autelitano D J
Baker Medical Research Institute, Melbourne, Victoria 8008, Australia.
Am J Physiol. 1999 Sep;277(3):G541-7. doi: 10.1152/ajpgi.1999.277.3.G541.
To evaluate the potential roles that both receptors and enzymes play in corticosteroid regulation of intestinal function, we have determined glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and 11beta-hydroxysteroid dehydrogenase (11beta-HSD) expression in intestinal epithelial cells. GR and MR mRNA and receptor binding were ubiquitously expressed in epithelial cells, with receptor levels higher in ileum and colon than jejunum and duodenum. RNase protection analysis showed that 11beta-HSD1 was not expressed in intestinal epithelial cells, and enzyme activity studies detected no 11-reductase activity. 11beta-HSD2 mRNA and protein were demonstrated in ileal and colonic epithelia; both MR and GR binding increased when enzyme activity was inhibited with carbenoxolone. Duodenal and jejunal epithelial cells showed very little 11beta-HSD2 mRNA and undetectable 11beta-HSD2 protein; despite minor (<7%) dehydrogenase activity in these cells, enzyme activity did not alter binding of corticosterone to either MR or GR. These findings demonstrate the ubiquitous but differential expression of MR and GR in intestinal epithelia and that 11beta-HSD2 modulates corticosteroid binding to both MR and GR in ileum and proximal and distal colon but not in duodenum or jejunum.
为评估受体和酶在皮质类固醇对肠道功能调节中所起的潜在作用，我们测定了肠道上皮细胞中糖皮质激素受体（GR）、盐皮质激素受体（MR）和11β-羟基类固醇脱氢酶（11β-HSD）的表达。GR和MR的mRNA及受体结合在上皮细胞中普遍表达，受体水平在回肠和结肠中高于空肠和十二指肠。核糖核酸酶保护分析表明，11β-HSD1在肠道上皮细胞中未表达，酶活性研究未检测到11-还原酶活性。在回肠和结肠上皮中证实了11β-HSD2的mRNA和蛋白；用甘珀酸抑制酶活性时，MR和GR的结合均增加。十二指肠和空肠上皮细胞显示出极少的11β-HSD2 mRNA且未检测到11β-HSD2蛋白；尽管这些细胞中有少量（<7%）脱氢酶活性，但酶活性并未改变皮质酮与MR或GR的结合。这些发现表明MR和GR在肠道上皮中普遍但差异表达，且11β-HSD2调节皮质类固醇与回肠、近端和远端结肠中MR和GR的结合，但在十二指肠或空肠中则不然。
