Metabolism of Oestrone Glucosiduronate at Midpregnancy

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.

Teratogenic Screening Methods and Their Application to Contraceptive Products

“…Diczfalusy: May I add some information to the data presented by Professor Tuch¬ mann-Duplessis on the transfer and metabolism of steroid conjugates in the human foetus and placenta? In situ perfusion studies with labelled conjugates indicate that the various types of oestrogen glucosiduronates are transferred from the foetus to the mother across the placenta, but that the rate of transfer is very slow (Levitz et al 1967;Zucconi et al 1967;Goebelsmann et al 1968). The transplacental passage of glucosiduronates is considerably slower than that of steroid sulphates, at least of the aryl sulphates and the 3-sulphates of the 3/5-hydroxy-Zl;i-steroids.…”

“…These two classes of steroid sulphates are rapidly hydrolyzed by the placenta and are transferred in part as unconjugated steroids. Placental hydrolysis is not essential for the transfer of steroid conjugates, since not only steroid glucosiduronates (Zucconi et al 1967;Goebelsmann et al 1968), but also certain steroid sulphates (Benagiano et al 1971) are transferred in an unchanged form.…”