Additional value of measurement of urinary cortisone and unconjugated cortisol metabolites in assessing the activity of 11 beta-hydroxysteroid dehydrogenase in vivo
Additional value of measurement of urinary cortisone and unconjugated cortisol metabolites in assessing the activity of 11 beta-hydroxysteroid dehydrogenase in vivo
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DOI：
10.1046/j.1365-2265.1997.2471061.x
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发表时间：
1997-08-01
影响因子：
3.2
通讯作者：
Walker, BR
中科院分区：
文献类型：
--
作者：
Best, R;Walker, BR
最近有研究表明，11 β -羟基类固醇脱氢酶（11 β - hsd）至少以2种同工酶的形式表达，在肝脏中，11 β - hsd1将可的松转化为皮质醇；在肾脏中，11 β - hsd2将皮质醇转化为可的松，对体内11 β - hsd活性的传统评估依赖于结合皮质醇和可的松代谢物的气相色谱测量。然而，这些方法不能区分酶的组织特异性活性，也不能反映所有形式的β - hsd缺乏症。在本报告中，我们评估了测量尿液中非共轭皮质醇代谢物、游离皮质醇和可的松作为人类肾脏β - hsd活性指标的有效性。设计6名钠平衡的健康男性受试者分别给予甘草次酸（170 mg，每天一次，以抑制11 β - hsd2）、卡贝诺酮(100 mg，每天一次，为了同时抑制11 β - hsd1和11 β - hsd2)或两种抑制剂联合使用，测量了尿电解质，并用气相色谱-质谱法测定了总和非共轭尿皮质醇及其代谢物的浓度。结果甘草次酸和卡贝诺酮对肾11 β - hsd2的抑制程度相似，通过相似的钠潴留来判断。如前所述，与卡贝诺洛酮相比，甘草次酸（比基线增加100-200%）对总皮质醇与可的松代谢物比率的常规测量受到更大程度的影响(
OBJECTIVE it has been shown recently that 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) is expressed as at least 2 isozymes, In the liver, 11 beta-HSD1 converts cortisone to cortisol; in the kidney, 11 beta-HSD2 converts cortisol to cortisone, Conventional assessment of 11 beta-HSD activity in vivo has relied on gas chromatographic measurement of the ratios of conjugated cortisol and cortisone metabolites. However, these do not permit distinction between the tissue-specific activities of the enzymes and do not reflect all forms of 11 beta-HSD deficiency, In this report, we have assessed the usefulness of measuring unconjugated cortisol metabolites and free cortisol and cortisone in urine as indices of renal 11 beta-HSD activity in man.DESIGN Six healthy male subjects established in sodium balance were given either glycyrrhetinic acid (170 mg t.d.s., to inhibit 11 beta-HSD2), carbenoxolone (100 mg t.d.s., to inhibit both 11 beta-HSD1 and 11 beta-HSD2) or both inhibitors in combination,MEASUREMENTS Urinary electrolytes were measured and the concentrations of total and unconjugated urinary cortisol and its metabolites were determined by gas chromatography mass spectrometry,RESULTS Glycyrrhetinic acid and carbenoxolone inhibited renal 11 beta-HSD2 to a similar degree, as judged by similar sodium retention. As previously reported, conventional measurement of ratios of total cortisol to cortisone metabolites were influenced to a greater extent by glycyrrhetinic acid (100-200% increase in ratio from baseline) than by carbenoxolone (