THE INCREASE IN URINARY-EXCRETION OF 6-BETA-HYDROXYCORTISOL AS A MARKER OF HUMAN HEPATIC CYTOCHROME-P450IIIA INDUCTION
THE INCREASE IN URINARY-EXCRETION OF 6-BETA-HYDROXYCORTISOL AS A MARKER OF HUMAN HEPATIC CYTOCHROME-P450IIIA INDUCTION
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DOI：
10.1111/j.1365-2125.1989.tb03516.x
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发表时间：
1989-10-01
影响因子：
3.4
通讯作者：
MAUREL, P
中科院分区：
文献类型：
--
作者：
GED, C;ROUILLON, JM;MAUREL, P
尿中排泄的6 β-羟基皮质醇，肝微粒体皮质醇6 β-对8 ~ 14例患者用利福平（600 mg/d，连用4天）治疗前后的血清羟化酶活性和细胞色素P450的含量进行了测定。利福平治疗使尿6 β-内酰胺酶的日排泄量平均增加5倍。羟皮质醇皮质醇6 β羟化酶活性从15 ± 0.01增加到15 ± 0.01。6 pmol min-1 mg-1，器官供体（视为“对照受试者”）至87 . ±.利福平治疗患者中为31 pmol min-1 mg-1。在三种形式的人P450（P450 IA，IIC和IIIA）中，（1），（2），通过蛋白质印迹法测定，只有P450 IIIA被抗生素显著诱导。只有抗P450 IIIA的抗体选择性抑制皮质醇6 β-人肝微粒体羟化酶。皮质醇6 β羟化酶活性与P450 Ⅲ A特异性含量相关。尿中6 β的水平羟基皮质醇与肝微粒体皮质醇6 β相关羟化酶和P450 IIIA特异性含量。我们得出结论，P450 IIIA主要负责皮质醇6 β。人肝微粒体和尿6 β-羟化酶活性羟基皮质醇是细胞色素P 450诱导的标志物。
Urinary excretion of 6.beta.-hydroxycortisol, hepatic microsomal cortisol 6.beta.-hydroxylase and the specific content of several forms of cytochrome P450 were measured in 8 to 14 patients before and after treatment with rifampicin (600 mg orally per day for 4 days). Rifampicin treatment produced an average five fold increase in daily excretion of urinary 6.beta.-hydroxycortisol. Cortisol 6.beta.-hydroxylase activity increased from 15 .+-. 6 pmol min-1 mg-1 in organ donors (considered as ''control subjects'') to 87 .+-. 31 pmol min-1 mg-1 in rifampicin treated patients. Among three forms of human P450 (P450IA, IIC and IIIA), (1), (2), measured by Western blots only P450IIIA was significantly induced by the antibiotic. Only antibodies against P450IIIA selectively inhibited cortisol 6.beta.-hydroxylase in human liver microsomes. Cortisol 6.beta.-hydroxylase was correlated with P450IIIA specific content. The urinary level of 6.beta.-hydroxycortisol correlated with liver microsomal cortisol 6.beta.-hydroxylase and P450IIIA specific content. We conclude that P450IIIA is predominantly responsible for cortisol 6.beta.-hydroxylase activity in human liver microsomes and that urinary 6.beta.-hydroxycortisol is a marker of the induction of this cytochrome P 450.