OESTRADIOL METABOLISM IN THE PREVIABLE HUMAN FOETUS AND IN THE FOETO-PLACENTAL UNIT.

Abstract

ABSTRACT Five normal previable foetuses were perfused with tracer amounts of oestradiol-4-14C and the metabolism of the compound was investigated. This study was completed by 3 experiments in which the oestradiol-4-14C was introduced in situ into the intact foeto-placental unit via the umbilical circulation. More than 80 per cent of the radioactive material present in the various foetal organs in both types of experiments was in a conjugated form. In contrast, in the placentas, less than 10 per cent of the total radioactivity present was in a conjugated form. The bulk of the radioactive material present in the foetal tissues was identified as oestradiol 3-sulphate and oestrone sulphate. In addition, two minor fractions were detected in the perfused foetuses, one of which behaved in countercurrent distribution studies as »glucosiduronates«; the other resembled »sulphates«. The oestrogen moiety of these two fractions was neither oestradiol nor oestrone, but it appeared to be a complex mixture. Although some radioactive material was found which closely resembled oestriol, it was not possible to detect oestriol with certainty. No glucosiduronate-like material was found in the foetal tissues following the injection of oestradiol-4-14C into the intact foeto-placental unit. Also the quantity of the »sulphate-like« material different from oestradioland oestrone sulphates was greatly reduced: A number of unconjugated metabolites were also detected, among which oestrone was identified. A perfusion experiment with an anencephalic foetus indicated that this foetus was capable of forming conjugated metabolites from oestradiol-4-14C. The results obtained do not favour the view that oestriol is a major and instantaneously formed foetal metabolite of oestradiol. On the other hand, they lend additional support to the concept that oestrogens reaching the foetus are extensively sulphurylated by the foetus and that these oestrogen sulphates are hydrolysed by the placenta before transfer of the oestrogen moiety to the maternal circulation.