Department of Surgery I, Miyazaki University Hospital, Kiyotake, Miyazaki 889 1692, Japan.
Steroids. 2010 Feb;75(2):164-8. doi: 10.1016/j.steroids.2009.11.006. Epub 2009 Dec 3.
The aim of this study was to investigate the effect of various bile acids on hepatic type I 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) activity in vitro. The rat liver microsome fraction was prepared and 11beta-HSD1 activity was assayed using cortisol and corticosterone as substrates for the enzyme reaction. The substrate and various concentrations of bile acids were added to the assay mixture. After incubation, the products were extracted and analyzed using high-performance liquid chromatography. All bile acids tested except deoxycholic acid and 7-keto bile acids inhibited the 11beta-HSD1 enzyme reaction to some degree. Ursodeoxycholic acid inhibited the activity less than cholic, chenodeoxycholic, and lithocholic acids. Deoxycholic acid and 7-keto bile acids did not inhibit, but enhanced the enzyme activity. Inhibitions of dehydrogenation by corticosterone were weaker than those by cortisol. Kinetic analysis revealed that the inhibition of 11beta-HSD1 was competitive. The inhibition of 11beta-HSD1 by bile acids depended on the three-dimensional structural difference in the steroid rings and the presence of the 7alpha-hydroxy molecule of the bile acids was important for the inhibition of rat hepatic 11beta-HSD1 enzyme activity. These results suggest that bile acid administration might modulate 11beta-HSD1 enzyme activity.
本研究旨在探讨各种胆汁酸对体外肝型 I 11β-羟甾类脱氢酶（11β-HSD1）活性的影响。制备大鼠肝微粒体部分，并使用皮质醇和皮质酮作为酶反应的底物来测定 11β-HSD1 活性。将底物和各种浓度的胆汁酸添加到测定混合物中。孵育后，使用高效液相色谱法提取并分析产物。除脱氧胆酸和 7-酮胆酸外，所有测试的胆汁酸均在某种程度上抑制 11β-HSD1 酶反应。熊脱氧胆酸的抑制活性小于胆酸、鹅脱氧胆酸和石胆酸。脱氧胆酸和 7-酮胆酸不抑制，但增强了酶活性。皮质酮对脱氢作用的抑制作用弱于皮质醇。动力学分析表明，抑制是竞争性的。胆汁酸对 11β-HSD1 的抑制取决于甾体环的三维结构差异，并且胆汁酸的 7α-羟基分子的存在对于抑制大鼠肝 11β-HSD1 酶活性很重要。这些结果表明，胆汁酸的给药可能调节 11β-HSD1 酶活性。
