Levin W, Thomas P E, Ryan D E, Wood A W
Department of Molecular Oncology, Roche Institute of Molecular Biology, Nutley, New Jersey 07110.
Arch Biochem Biophys. 1987 Nov 1;258(2):630-5. doi: 10.1016/0003-9861(87)90386-9.
In the present study we show that monospecific antibody against cytochrome P-450a completely inhibits testosterone 7 alpha-hydroxylation in hepatic microsomes of untreated male or female rats or rats of either sex treated with dexamethasone. These data are in contrast with those of K. Nagata et al. (1987, J. Biol. Chem. 262, 2787-2793) who recently reported that an antibody prepared against cytochrome P-450a completely inhibited testosterone 7 alpha-hydroxylase activity in microsomes from untreated or 3-methylcholanthrene-treated rats but only inhibited 50% of the activity in microsomes from dexamethasone-treated rats. They proposed that dexamethasone treatment of rats induced another testosterone 7 alpha-hydroxylase in rat liver. The discrepancy in the two sets of data was due, at least in part, to the use of a chromatography system by Nagata et al. that is incapable of resolving a number of testosterone metabolites. Dexamethasone treatment of rats leads to a marked increase in the production of several testosterone metabolites, including 15 beta-hydroxytestosterone which is cochromatographic with 7 alpha-hydroxytestosterone in their chromatography system. Our results indicate that cytochrome P-450a accounts for all of the testosterone 7 alpha-hydroxylase activity in microsomes from dexamethasone-treated rats, and that testosterone 7 alpha-hydroxylation continues to be a useful marker for monitoring cytochrome P-450a in rat hepatic microsomes.
在本研究中，我们发现，针对细胞色素P - 450a的单特异性抗体可完全抑制未处理的雄性或雌性大鼠，或用地塞米松处理的任一性别的大鼠肝微粒体中的睾酮7α-羟化作用。这些数据与K. Nagata等人（1987年，《生物化学杂志》262卷，2787 - 2793页）的结果相反，他们最近报道，针对细胞色素P - 450a制备的抗体可完全抑制未处理的或经3 - 甲基胆蒽处理的大鼠微粒体中的睾酮7α-羟化酶活性，但仅抑制经地塞米松处理的大鼠微粒体中50%的活性。他们提出，用地塞米松处理大鼠会诱导大鼠肝脏中另一种睾酮7α-羟化酶。两组数据的差异至少部分是由于Nagata等人使用的色谱系统无法分离多种睾酮代谢物。用地塞米松处理大鼠会导致几种睾酮代谢物的产生显著增加，包括15β-羟基睾酮，在他们的色谱系统中，其与7α-羟基睾酮共色谱。我们的结果表明，细胞色素P - 450a解释了经地塞米松处理的大鼠微粒体中所有的睾酮7α-羟化酶活性，并且睾酮7α-羟化作用仍然是监测大鼠肝微粒体中细胞色素P - 450a的一个有用标志物。
