Simultaneous perfusion of [4-14C]oestriol and [6,9-3H2]oestriol 16 alpha-monoglucuronide through the isolated rat liver. I. Qualitative aspects.

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.