Lund B O, Lund J
Department of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala.
J Biol Chem. 1995 Sep 8;270(36):20895-7. doi: 10.1074/jbc.270.36.20895.
Adrenocortical mitochondrial cytochrome P450 isozymes of the Cyp11 family normally synthesize steroids with a very strict substrate specificity. However, for the first time, P450c11 was additionally shown to metabolize and bioactivate the adrenotoxic environmental pollutant 3-methylsulfonyl-2,2-bis(4-chlorophenyl)-1,1-dichloroethene (MeSO2-DDE). This conclusion is based on a striking correlation between inductions of MeSO2-DDE and deoxycorticosterone metabolism by forskolin in the adrenocortical cell lines Y1 and Kin-8, inhibition of P450c11-dependent activities in Y1 cells by MeSO2-DDE, and metabolism of MeSO2-DDE by non-steroidogenic COS cells after transfection with a cDNA encoding P450c11. The interaction between xenobiotics and glucocorticoid synthesis should focus more attention to xenobiotic-induced hormonal disturbances.
Cyp11家族的肾上腺皮质线粒体细胞色素P450同工酶通常以非常严格的底物特异性合成类固醇。然而，首次发现P450c11还能代谢并生物激活肾上腺毒性环境污染物3-甲基磺酰基-2,2-双（4-氯苯基）-1,1-二氯乙烯（MeSO2-DDE）。这一结论基于在肾上腺皮质细胞系Y1和Kin-8中，福斯可林对MeSO2-DDE的诱导与脱氧皮质酮代谢之间的显著相关性、MeSO2-DDE对Y1细胞中P450c11依赖性活性的抑制，以及用编码P450c11的cDNA转染非类固醇生成性COS细胞后MeSO2-DDE的代谢。外源性物质与糖皮质激素合成之间的相互作用应更关注外源性物质引起的激素紊乱。
