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Evaluation of in vivo enzymatic activity of cortisol metabolism associated with hypertension

与高血压相关的皮质醇代谢的体内酶活性评估

基本信息

批准号：
09672338
负责人：
KASUYA Yasuji
金额：
$ 1.92万
依托单位：
Tokyo University of Pharmacy and Life Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672338/
关键词：
cortisol cortisone stabel isotope methodology 11β-HSD actitity urinary cortisone cortisol ratio hypertension GC-MS-SIM pharmacokinetics 重水素標識コルチゾール重水素標識コルチゾン GC-MS分析速度論的解析尿中代謝物ヒトin vivo酵素活性 GC-MS 分析ヒト in vivo 酵素活性高血

项目摘要

One of the most unique advatages of the use of isotopically labeled compounds as tracers is that an endogenous compound and its exogenously administered stable isotopically labeled analog are separately measurable by using mass spectrometry.This study is associated with a new approach using stable isotope methodology in evaluating 11β-HSD activities in vivo based on urinary excretion of unconjugated cortisol and cortisone. The method involved the measurement of stable isotopically labeled cortisol with ィイD12ィエD1H and its labeled metabolite, cortisone-ィイD12ィエD1H by GC-MS simultaneously with endogenous cortisol and cortisone after oral administration of a few mg of ィイD12ィエD1H-labeled cortisol to normal human subjects.This stable isotope approach offered unique advantages since it allowed to measure stable isotopically labeled cortisol and its labeled metabolite cortisone simultaneously with endogenous (unlabeled) cortisol and cortisone. Very important was the potential use of stable isotopically labeled cortisol in man as a tracer for the native cortisol to recognize the conversion of cortisol to cortisone in the kidney. Our results from the stable isotope methodology strongly suggest that the measurement of unconjugated cortisol and cortisone in urine is a significant advance in assessing renal 11β-HSD2 activity in man.

同位素标记化合物作为示踪剂的最大优点之一是内源性化合物和外源性稳定同位素标记化合物可分别用质谱法测定，本研究基于尿中未结合的皮质醇和可的松的排泄，提出了一种用稳定同位素方法评价11β-HSD体内活性的新方法。该方法涉及用β-D12-β-D1 H及其标记代谢物测量稳定同位素标记的皮质醇，口服几mg可的松D12 β D1 H后，通过GC-MS同时测定可的松-β D12 β D1 H和内源性皮质醇和可的松-β D12 β D1 H。这种稳定的同位素方法提供了独特的优势，因为它允许测量稳定的同位素标记的皮质醇及其标记的代谢物可的松与内源性（未标记的）皮质醇和可的松同时。非常重要的是，稳定的同位素标记的皮质醇在人体中的潜在用途，作为天然皮质醇的示踪剂，以识别皮质醇在肾脏中转化为可的松。我们的稳定同位素方法学结果强烈表明，尿液中未结合的皮质醇和可的松的测量是评估人体肾脏11β-HSD 2活性的一个重大进展。