3-MONOGLUCURONYL-GLYCYRRHETINIC ACID IS A MAJOR METABOLITE THAT CAUSES LICORICE-INDUCED PSEUDOALDOSTERONISM
3-MONOGLUCURONYL-GLYCYRRHETINIC ACID IS A MAJOR METABOLITE THAT CAUSES LICORICE-INDUCED PSEUDOALDOSTERONISM
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DOI：
10.1210/jc.80.6.1929
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发表时间：
1995-06-01
影响因子：
5.8
通讯作者：
KOBAYASHI, M
中科院分区：
文献类型：
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作者：
KATO, H;KANAOKA, M;KOBAYASHI, M
18 β-甘草次酸（GA）被认为是导致甘草诱导的假醛固酮增多症的主要代谢产物之一。然而，我们没有发现有和没有假性醛固酮增多症的患者之间的GA的血液水平的差异。我们通过高效液相色谱法测定了3 β-D-（单葡萄糖醛酸基）18 β-大黄酸（3 MGA）（3 β-D-二葡萄糖醛酸基-18 β-大黄酸（大黄素）的另一种代谢产物）的血药浓度，发现10名甘草诱导的假性醛固酮增多症患者的3 MGA浓度升高，但11名非假性醛固酮增多症患者的3 MGA浓度未升高。为了研究3 MGA是否能抑制11 β-羟基类固醇脱氢酶，我们孵育大鼠肾微粒体与或不与3 MGA和测量[H-3]皮质醇转化率[H-3]可的松。发现3 MGA是11 β-羟基类固醇脱氢酶的有效抑制剂，允许皮质醇发挥其全部盐皮质激素作用。这些结果表明，甘草诱导的假性醛固酮增多症是由于这些患者的循环血液中3 MGA浓度增加，而不是GA。
18 beta-Glycyrrhetinic acid (GA) has been thought to be one of the major metabolites that causes licorice-induced pseudoaldosteronism. However, we found no difference in the blood level of GA between the patients with and without pseudoaldosteronism. We measured the blood concentration of 3 beta-D-(monoglucuronyl)18 beta-glycyrrhetinic acid (3MGA), another metabolite of 3 beta-D-diglucuronyl-18 beta-glycyrrhetinic acid (glycyrrhizin), by high performance liquid chromatography and found an increased concentration of 3MGA in 10 patients with licorice-induced pseudoaldosteronism, but not in 11 patients without pseudoaldosteronism. To investigate whether 3MGA can inhibit 11 beta-hydroxysteroid dehydrogenase, we incubated rat renal microsome with or without 3MGA and measured the conversion rate of [H-3]cortisol to [H-3]cortisone. 3MGA was found to be a potent inhibitor of 11 beta-hydroxysteroid dehydrogenase, allowing cortisol to exert its full mineralocorticoid effects. These results suggest that licorice-induced pseudoaldosteronism is due to an increased concentration of 3MGA, but not GA, in the circulating blood of these patients.