METABOLISM OF OESTRONE GLUCOSIDURONATE AT MIDPREGNANCY

Abstract

ABSTRACT Oestrone-6,7-3H-glucosiduronate-14C (OE1-3H-Gl-14C) has been prepared biosynthetically and its metabolism studied in two cases of therapeutic abortion following the administration of the tracer at laparotomy into the umbilical vein. The bulk of the radioactive material recovered was in the foetus and placenta; only small amounts were present in the urine of the mother. Minute quantities of the radioactive material recovered from any of these sources were in an unconjugated form. Following reduction with KBH4 of the extract of the foetal liver oestriol-3-glucosiduronate (OE3-3Gl) was isolated from this source with the same isotopic ratio as that of the injected material. Following hydrolysis with β-glucuronidase, 3H-labelled oestrone, 17β-oestradiol and oestriol were isolated in a radiochemically homogeneous form from the foetal liver and from the urine of the mother, and oestrone and 17β-oestradiol from the placenta. From the urine of the mothers OE1-3H-Gl-14C was also isolated. It exhibited the same isotopic ratio as the injected material. Following the intravenous infusion to two women at midpregnancy of a combination of 3H-labelled OE1-Gl and 14C-labelled oestrone sulphate (OE1-S), the tracer administered as OE1-Gl was eliminated in the urine far more rapidly than that infused in the form of OE1-S. It is concluded that at midpregnancy a) the foetus is capable of metabolizing OE1-Gl without any preceding hydrolysis, b) the placenta exhibits no β-glucuronidase activity, c) only a limited amount of OE1-Gl is transferred from the foeto-placental circulation to the mother and exclusively in an unchanged form, and d) OE1-Gl is eliminated from the maternal circulation much more rapidly than OE1-S.