Höller M, Weber H, Breuer H
Acta Endocrinol (Copenh). 1982 May;100(1):57-62.
Equimolar concentrations of [4-14C]oestriol and [6,9-3H]oestriol 16 alpha-monoglucuronide were simultaneously perfused through isolated rat livers. Oestriol was hydroxylated to 2-hydroxyoestriol and 6 xi-hydroxyoestriol; 2-hydroxyoestriol was further methylated to 2-methoxyoestriol. Oxidoreduction of oestriol led to the formation of 16 alpha-hydroxyoestrone, 16-0xooestradio-17 beta and 16-epioestriol. In addition, two dehydroxylation products, namely oestrone and oestradiol-17 beta were found. The metabolites formed from oestriol were partly conjugated to monoglucuronides, monosulphates and sulphoglucuronides. About 80% of the oestriol perfused was hydroxylated at C-atom 2. Most of the 2-hydroxyoestriol formed was either methylated (about 37%) or sulphated (about 55%). Only small amounts (less than 2%) of the catecholoestrogens formed were methylated as well as sulphated. The 2-hydroxyoestriol monosulphates accumulated in the liver. After their conjugation with glucuronic acid, the double conjugates formed were immediately excreted into the bile. In fact, 2-hydroxyoestriol 16 alpha-monoglucuronide 2(3?)-monosulphate comprised by far the main biliary metabolite of [4-14C]oestriol, followed by oestriol 16 alpha-monoglucuronide and 2-methoxyoestriol 16 alpha-monoglucuronide. No triated sulphoglucuronides were detected, thus indicating that the monosulphates are the immediate precursors of the double conjugates. [6,9-3H2]Oestriol 16 alpha-monoglucuronide was metabolised only to a small extent. After its uptake into the liver more than 90% of this conjugate was secreted unchanged into the bile. The remaining part was hydrolysed; the oestriol liberated followed the same metabolic reactions as those found for [4-14C]oestriol. This indicates that the 16 alpha-glucuronide of oestriol is not metabolised to any appreciable extent.
将等摩尔浓度的[4-¹⁴C]雌三醇和[6,9-³H]雌三醇16α-单葡萄糖醛酸苷同时灌注通过离体大鼠肝脏。雌三醇被羟基化为2-羟基雌三醇和6ξ-羟基雌三醇；2-羟基雌三醇进一步甲基化为2-甲氧基雌三醇。雌三醇的氧化还原反应导致形成16α-羟基雌酮、16-氧代雌二醇-17β和16-表雌三醇。此外，还发现了两种脱羟基产物，即雌酮和雌二醇-17β。雌三醇形成的代谢产物部分与单葡萄糖醛酸苷、单硫酸盐和硫酸葡萄糖醛酸苷结合。灌注的雌三醇中约80%在2位碳原子上被羟基化。形成的大部分2-羟基雌三醇要么被甲基化（约37%）要么被硫酸化（约55%）。形成的儿茶酚雌激素只有少量（不到2%）同时被甲基化和硫酸化。2-羟基雌三醇单硫酸盐在肝脏中积累。它们与葡萄糖醛酸结合后，形成的双结合物立即排入胆汁。实际上，2-羟基雌三醇16α-单葡萄糖醛酸苷2(3ʹ)-单硫酸盐是[4-¹⁴C]雌三醇迄今为止主要的胆汁代谢产物，其次是雌三醇16α-单葡萄糖醛酸苷和2-甲氧基雌三醇16α-单葡萄糖醛酸苷。未检测到³H标记的硫酸葡萄糖醛酸苷，因此表明单硫酸盐是双结合物的直接前体。[6,9-³H₂]雌三醇16α-单葡萄糖醛酸苷仅在很小程度上被代谢。它被肝脏摄取后，超过90%的这种结合物未发生变化就分泌到胆汁中。其余部分被水解；释放出的雌三醇遵循与[4-¹⁴C]雌三醇相同的代谢反应。这表明雌三醇的16α-葡萄糖醛酸苷没有被显著代谢。
