Tresca J P, Ponsard G, Degrelle H
Can J Biochem. 1982 May;60(5):549-55.
The incubation of PE2 ((6,7-3H)-labelled 3-propyl ether of estra-1,3,5(10)triene-3, 17 beta-diol (estradiol)) with various subcellular fractions of rat liver indicated that the hepatic metabolism of this compound occurs mainly in the microsomal fraction. In addition to the formation of 3-propyl ethers of estra-1,3,5(10)triene-3-ol-17-one (estrone) and estra-1,3,5(10-triene-3, 16alpha, 17 beta-triol (estriol) directly deriving from PE2, the microsomal proteins carried out the deetherification of the propyl ether group leading to phenolic steroids; among them, estradiol, estrone, and estriol were characterized. Protein-bound and water-soluble metabolites were found; the effects of glutathione and of the incubation conditions were in agreement with the thioconjugation of these derivatives. The microsomal metabolism of PE2, and specially the deetherification reaction, required the presence of oxygen and of NADPH as cofactor, the optimum pH ranging from 7.4 to 8. The participation of cytochrome P450 in these metabolic pathways was shown by a partially inhibited catabolism with carbon monoxide and by a more active metabolism in males than in females and when animals were pretreated with phenobarbital. These results allowed us to conclude that the hepatic deetherification of PE2 is carried out by a microsomal oxidative system which is very similar to the system involved in the demethylation of methyl ethers of estrogens.
用（6,7-³H）标记的雌甾-1,3,5（10）-三烯-3,17β-二醇（雌二醇）的3-丙基醚（PE2）与大鼠肝脏的各种亚细胞组分进行温育，结果表明该化合物的肝脏代谢主要发生在微粒体组分中。除了直接由PE2形成雌甾-1,3,5（10）-三烯-3-醇-17-酮（雌酮）的3-丙基醚和雌甾-1,3,5（10）-三烯-3,16α,17β-三醇（雌三醇）外，微粒体蛋白还使丙基醚基团脱醚化，生成酚类甾体；其中，已对雌二醇、雌酮和雌三醇进行了表征。发现了与蛋白结合的代谢产物和水溶性代谢产物；谷胱甘肽和温育条件的影响与这些衍生物的硫醚共轭作用一致。PE2的微粒体代谢，特别是脱醚化反应，需要氧气和NADPH作为辅因子，最适pH范围为7.4至8。一氧化碳对分解代谢的部分抑制以及雄性动物比雌性动物以及用苯巴比妥预处理的动物代谢更活跃，表明细胞色素P450参与了这些代谢途径。这些结果使我们得出结论，PE2的肝脏脱醚化是由一个微粒体氧化系统进行的，该系统与参与雌激素甲基醚去甲基化的系统非常相似。
