Use of 11α-deuterium labeled cortisol as a tracer for assessing reduced 11β-HSD2 activity in vivo following glycyrrhetinic acid ingestion in a human subject
Use of 11α-deuterium labeled cortisol as a tracer for assessing reduced 11β-HSD2 activity in vivo following glycyrrhetinic acid ingestion in a human subject
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DOI：
10.1016/j.steroids.2004.10.006
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发表时间：
2005-02-01
期刊：
影响因子：
2.7
通讯作者：
Furuta, T
中科院分区：
文献类型：
--
作者：
Kasuya, Y;Yokokawa, A;Furuta, T
本研究描述了口服5 mg [1，2，4，19-C-13（4），11 α-H-2]皮质醇（皮质醇-C-13（4），H-2（1）），一个单独使用皮质醇-C-13（4），H-2（1），另一个使用皮质醇-C-13（4），H-2（1）加130 mg/天的大黄酸，持续6天。所采用的稳定同位素方法允许评价11 β-羟基类固醇脱氢酶（11 β-HSD）的两种同工酶（11 β-HSD 1和11 β-HSD 2）的个体体内活性，并证明皮质醇消除半衰期变化对检测大黄酸诱导的11 β-HSD 2活性抑制的灵敏度。与11 β-HSD 2将皮质醇-C-13（4）、H-2（1）转化为可的松-C-13（4）过程中11 α-H-2损失相关的动力学分析清楚地表明，摄入大黄酸后，11 β-HSD 2活性降低，如皮质醇-C-13（4）、H-2（1）消除半衰期增加所示。皮质醇-C-13（4）、H-2（1）的消除半衰期为11 β-HSD 2活性提供了灵敏的体内测量方法，并且对于检测肾脏11 β-HSD 2活性的变化比游离皮质醇和游离可的松的尿液比率（UFF/UFE）的测量更灵敏。在皮质醇的11 α-位的H-2-标记作为一个适当的示踪剂，用于评估降低的11 β-HSD 2活性在体内由大黄酸诱导。(C)2004年爱思唯尔公司All rights reserved.
This study describes an oral administration of 5 mg of [1,2,4,19-C-13(4),11alpha-H-2]cortisol (cortisol-C-13(4),H-2(1)) to a human subject performed on two separate occasions, one with cortisol-C-13(4),H-2(1) alone and the other with Cortisol-C-13(4),H-2(1) plus 130 mg per day of glycyrrhetinic acid for 6 days. The stable isotope methodology employed allowed for the evaluation of the individual in vivo activities of the two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD), 11beta-HSD1 and 11beta-HSD2, and to demonstrate the sensitivity of changes in cortisol elimination half-life for detecting inhibition of 11beta-HSD2 activity induced with glycyrrhetinic acid. The kinetic analysis associated with the loss of 11alpha-H-2 during the conversion of Cortisol-C-13(4),H-2(1) to cortisone-C-13(4) by 11beta-HSD2 clearly indicated reduced 11beta-HSD2 activity with glycyrrhetinic acid ingestion, as observed by an increase in the elimination half-life of cortisol-C-13(4),H-2(1). The elimination half-life of cortisol-C-13(4),H-2(1) provided sensitive in vivo measures of 11beta-HSD2 activity and was more sensitive for detecting changes in renal 11beta-HSD2 activity than the measurement of the urinary ratio of free cortisol and free cortisone (UFF/UFE). The H-2-labeling in the 11alpha-position of cortisol served as an appropriate tracer for assessing the reduced 11beta-HSD2 activity in vivo induced by glycyrrhetinic acid. (C) 2004 Elsevier Inc. All rights reserved.