Effect of hypophysectomy and growth hormone replacement on the modulation of p450 expression after treatment with the aromatic hydrocarbon ethylbenzene.
Effect of hypophysectomy and growth hormone replacement on the modulation of p450 expression after treatment with the aromatic hydrocarbon ethylbenzene.
复制标题
垂体切除术和生长激素替代对芳香烃乙苯治疗后 p450 表达调节的影响。
DOI：
10.1006/taap.2001.9145
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发表时间：
2001
影响因子：
3.8
通讯作者：
Backes,WL
中科院分区：
文献类型：
--
作者：
Serron,SC;Zhang,S;Bergeron,RM;Backes,WL
P450状态对几种细胞色素P450酶的表达有显著影响。本研究的目的是研究垂体输入的作用，调节CYP 2C 11和CYP 2B后，与芳香烃类化合物（EB）的治疗。完整的，垂体切除（HX），HX大鼠补充脉动生长激素（GH）与玉米油或EB和肝P450表达的影响进行了测定。垂体切除导致未治疗大鼠的CYP 2C 11蛋白减少50%，而GH补充使蛋白恢复至对照水平。EB给药也降低了完整大鼠的CYP 2C 11蛋白;然而，在HX或HX + GH组中，EB给药后未观察到这种降低。CYP 2C 11依赖性睾酮2α-羟基化遵循与CYP 2C 11蛋白相似的模式，不同之处在于GH替代仅部分恢复活性。CYP 2B水平也受到垂体切除术的显著影响。完整的大鼠表现出100倍的CYP 2B 1 mRNA的增加，达到最大值后12小时，EB管理。更小的反应（约。20倍），EB处理后24小时达到最大值。这种效应并没有被GH补充逆转。EB的半衰期显着增加，从8小时在完整的大鼠到14小时在HX大鼠，表明更高的血浆EB浓度后，EB给药HX大鼠。这些结果表明，CYP 2C 11和CYP 2B成为HX大鼠EB依赖性调制的反应，不能简单地解释为GH的情况下，或通过改变HX动物EB药代动力学的反应。
Pituitary status has a significant effect on the expression of several cytochrome P450 enzymes. The goal of this study was to examine the role of pituitary input on the modulation of CYP2C11 and CYP2B after treatment with the aromatic hydrocarbon ethylbenzene (EB). Intact, hypophysectomized (HX), and HX rats supplemented with pulsatile growth hormone (GH) were treated with corn oil or EB and the effects on hepatic P450 expression were determined. Hypophysectomy caused a 50% decrease in CYP2C11 protein in untreated rats, whereas GH supplementation returned protein to control levels. EB administration also decreased CYP2C11 protein in intact rats; however, this decrease was not observed after EB treatment in HX or HX + GH groups. CYP2C11-dependent testosterone 2α-hydroxylation followed a similar pattern as CYP2C11 protein, except that the activity was only partially restored by GH replacement. CYP2B levels were also substantially influenced by hypophysectomy. Intact rats exhibited a 100-fold increase in CYP2B1 mRNA, reaching a maximum 12 h after EB administration. A much smaller response (ca. 20-fold) was observed in HX rats, reaching a maximum 24 h after EB treatment. This effect was not reversed by GH supplementation. The half-life for EB was significantly increased from 8 h in intact rats to 14 h in HX rats, suggesting higher plasma EB concentrations after EB administration to HX rats. These results indicate that CYP2C11 and CYP2B become less responsive to EB-dependent modulation in HX rats, a response that cannot be explained simply by absence of GH or by altered EB pharmacokinetics in HX animals.