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

• 批准号: 16590126
• 负责人: KASUYA Yasuji
• 金额: $ 2.24万
• 依托单位: Tokyo University of Pharmacy and Life Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590126/
• 关键词: cortisol; cortisone; stable isotope methodology; 11β-activity; urinary cortisone; cortisol ratio; renal disease; hypertension; GC-MS-SIM; グリチルリチン酸; 体内動態; 速度論的解析; 安定同位体標識; 11β-HSD2酵素活性評価

This study is associated with a unique approach using stable isotope methodology in evaluating 11β-HSD2 activity in vivo based on urinary excretion of unconjugated (free) cortisol and cortisone. This stable isotope approach offered useful advantages since it allowed to measure stable isotopically labeled cortisol and its labeled metabolite cortisone 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 free cortisol and cortisone in urine is a significant advantage in assessing renal 1lb-HSD2 activity in man.The kidney is a major site for the conversion of cortisol to cortisone. Since the urinary free cortisone/ cortisol ratio has been proved to be a specific in vivo measure of 11β-HSD2 activity in human kidney reflecting intra-renal concentrations of cortisol and cortisone, a further study was performed to recognize the conversion of cortisol to cortisone catalized by 11β-HSD2 in patients with renal disease.This study provided direct evidence with regard to the usefulness of a urinary free cortisone/cortisol ratio as an index of human clinical tests for evaluating a reduced 11β-HSD2 activity.

这项研究与一种独特的方法有关，该方法使用稳定同位素方法，根据未结合（游离）皮质醇和可的松的尿排泄来评价体内11β-HSD 2活性。这种稳定的同位素方法提供了有用的优势，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的潜在用途的稳定同位素标记的皮质醇在人作为示踪剂的天然皮质醇，以识别皮质醇转化为可的松在肾脏。我们的结果从稳定同位素方法强烈表明，游离皮质醇和可的松在尿中的测量是一个显着的优势，在评估肾脏1 lb-HSD 2活性的人。肾脏是一个主要的网站皮质醇可的松的转换。由于尿游离可的松/可的松比率已被证明是人体肾脏中11β-HSD 2活性的特异性体内测量，反映了皮质醇和可的松的肾内浓度，进行了进一步的研究，以确认肾脏疾病患者中11β-HSD 2催化的皮质醇转化为可的松。这项研究提供了关于尿游离可的松/皮质醇比率作为评估降低的11β-HSD 2活性的人体临床试验的指标。

项目成果

Use of 11 a-deuterium labeled cortisol as a tracer for assessing reduced 11 β-HSD2 activity in vivo following glycyrrhetinic acid ingestion in a human subject.

使用 11α-氘标记的皮质醇作为示踪剂，用于评估人类受试者摄入甘草次酸后体内 11β-HSD2 活性降低的情况。

• 发表时间: 2005
• 期刊: Steroids 70-2
• 作者: Y.Kasuya;A.Yokokawa;S.Takashima;H.Shibasaki;T.Futruta
• 通讯作者: T.Futruta

Validation of the plasma half-life of 11α-deuterium cortisol as a sensitive indexr for the analysis of 11β-HSD2 activity in vivo.

验证 11α-氘皮质醇的血浆半衰期作为分析体内 11β-HSD2 活性的敏感指标。

• 发表时间: 2005
• 期刊: Steroids 70・12
• 作者: Kasuya Y;Yokokawa A;Hamura K;Shibasaki H;Furuta T
• 通讯作者: Furuta T

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

• DOI: 10.1016/j.steroids.2004.10.006
• 发表时间: 2005-02-01
• 期刊: STEROIDS
• 影响因子: 2.7
• 作者: Kasuya, Y;Yokokawa, A;Furuta, T
• 通讯作者: Furuta, T

Validation of the plasma half-life of 11α-deuterium cortisol as a sensitive index for the analysis of human 11β-HSD2 activity in vivo.

验证 11α-氘皮质醇的血浆半衰期作为分析人体内 11β-HSD2 活性的敏感指标。

• 发表时间: 2005
• 期刊: Steroids 70・12
• 作者: Shino Nakamura;Kikuoka;Yasuji Kasuya
• 通讯作者: Yasuji Kasuya

Validation of the plasma half-life of 1la-deuterium cortisol as a sensitive index for the analysis of human 11β-HSD2 activity in vivo.

验证 1la-氘皮质醇的血浆半衰期作为分析人体内 11β-HSD2 活性的敏感指标。

• 发表时间: 2005
• 期刊: Steroids 70-12
• 作者: Y.Kasuya;A.Yokokawa;K.Hamura;H.Shibasaki;T.Futruta
• 通讯作者: T.Futruta