Simultaneous perfusion of [4-14C]oestriol and [6,9-3H2]oestriol 16α-monoglucuronide through the isolated rat liver

Abstract

Abstract. The uptake of [4-14C]oestriol by the isolated perfused rat liver is 3.8 times faster as compared to that of simultaneously perfused [6,9-3H2]oestriol 16α-monoglucuronide. During perfusion the concentration of both radioactive oestrogens decreased exponentially in perfusion medium (apparent kel: 0.061 min−1 and 0.016 min−1, respectively). [6,9−3H2]Oestriol 16α-monoglucuronide was metabolized only to a small extent; more than 92% was secreted unchanged into the bile where it was highly concentrated (1800 nmol/g). In contrast [4-14C]oestriol was extensively metabolized; it was mainly hydroxylated at C-atom 2, leading to a rapid increase in the concentration of 2-hydroxyoestriol in the perfused medium. This metabolite was quickly taken up by the liver during recirculation and subsequently either methylated or sulphated. 2-Hydroxyoestriol monosulphate was glucuronated to 2-hydroxyoestriol 16α-monoglucuronide 3-sulphate, which was rapidly excreted into the bile. No double conjugate was formed when [6,9-3H2]oestriol 16α-monoglucuronide was perfused; this is additional evidence for the correctness of the assumption that monoglucuronides cannot serve as precursors of sulphoglucuronides.