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芳烃介导的CYP2B和CYP2C11表达中的垂体成分。

Pituitary component of the aromatic hydrocarbon-mediated expression of CYP2B and CYP2C11.

作者信息

Bergeron R M, Serron S C, Rinehart J J, Cawley G F, Backes W L

机构信息

Department of Pharmacology and Experimental Therapeutics, The Stanley S. Scott Cancer Center, Louisiana State University Medical Center, New Orleans 70112, USA.

出版信息

Xenobiotica. 1998 Mar;28(3):303-12. doi: 10.1080/004982598239588.

Abstract
  1. The aim was to determine if the ethylbenzene (EB)-mediated expression of CYP2B and CYP2C11 involved a hormonally controlled component. 2. The hypophysectomized (HX) and intact rats were treated with EB for 1 or 2 days, and the effects on specific CYP levels measured. 3. Differences were observed in the inducibility of CYP2B by EB in the HX rat when compared with intact controls. Whereas significant elevations of CYP2B-dependent activities and protein levels were observed after both 1 and 2 days of EB injection in intact controls, CYP2B levels were significantly elevated in the HX rat only after 2 days of hydrocarbon treatment. 4. Both CYP2C11-dependent activities and protein levels were decreased after EB administration to the intact rat. In contrast, CYP2C11 levels were unaffected by EB in the HX rat at any of the time points indicated. 5. CYP2C11 protein levels were unaffected by treatment with EB for 24 h in cultured hepatocytes, also supporting the hypothesis that hormones are involved in CYP2C11 expression. 6. This study indicates that pituitary input influences the EB-mediated changes in both CYP2B and CYP2C11. CYP2C11 is affected by EB administration in a manner similar to other xenobiotics such as phenobarbital. On the other hand, the smaller induction of CYP2B1/2 in response to EB differs from that observed with phenobarbital where HX augmented the response of the inducer.
摘要
  1. 目的是确定乙苯(EB)介导的CYP2B和CYP2C11表达是否涉及激素控制成分。2. 对垂体切除(HX)大鼠和完整大鼠用EB处理1天或2天,并测量对特定CYP水平的影响。3. 与完整对照相比,观察到HX大鼠中EB对CYP2B的诱导性存在差异。在完整对照中,EB注射1天和2天后均观察到CYP2B依赖性活性和蛋白水平显著升高,而在HX大鼠中,仅在烃处理2天后CYP2B水平才显著升高。4. 对完整大鼠给予EB后,CYP2C11依赖性活性和蛋白水平均降低。相反,在所示的任何时间点,HX大鼠中的CYP2C11水平均不受EB影响。5. 在培养的肝细胞中,用EB处理24小时对CYP2C11蛋白水平无影响,这也支持了激素参与CYP2C11表达的假说。6. 本研究表明垂体输入影响EB介导的CYP2B和CYP2C11的变化。CYP2C11受EB给药的影响方式与其他异种生物如苯巴比妥相似。另一方面,EB诱导的CYP2B1/2的较小诱导与苯巴比妥观察到的不同,苯巴比妥中HX增强了诱导剂的反应。

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