Fetal and Maternal Metabolism of Estradiol During Pregnancy

Abstract

The fetal and maternal metabolism of estradiol (E2) was studied by isotope dilution methods involving the administration of tracers of E2 and the measurement of the specific activities of urinary metabolites. In one experiment, tritiated E2 was introduced into the peritoneal cavity of the fetus during a transfusion, in utero, for erythroblastosis fetalis. In 3 other pregnant women, 3H-E2 was administered intra-amniotically. In all experiments, simultaneously with the administration of the tritiated tracer, 14C-E2 was injected into a maternal peripheral vein. Urine collected following the injections was treated with β-glucuronidase and estrone, estradiol, epiestriol, estriol and a metabolite more polar than estriol (a tetrol, E4) were isolated. E4 contained little or no 14C, thus revealing its fetal origin. Formulae derived from a theoretical analysis of tracer experiments were used to estimate the rates at which E2 formed in the placenta is released into the fetal and maternal circulations and the rates of transfer of E2 between mother and fetus. In the experiment in which 3H-E2 was administered directly into the fetus, 10% of the urinary estriol was estimated to be derived from maternally circulating E2, 4% from fetal metabolism of E2 and 86 % from other precursors.