METABOLISM OF OESTRONE AND OESTRADIOL IN THE HUMAN FOETO-PLACENTAL UNIT AT MIDPREGNANCY

Abstract

In 4 cases of therapeutic abortion by laparotomy, tracer amounts of estrone-6,7-H3 and 17[beta]-estradiol-16-C14 were injected into the umbilical vein 20 min. prior to the interruption of gestation, and the radioactive material recovered from the placenta and various fetal tissues was analysed. More than 92% of the radioactive material recovered from the fetus, but less than 15% of that present in the placenta, was in a conjugated form. Among the fetal tissues studied, the highest percentage of unconjugated (free) radioactive material (25%) occurred in the adrenals. Determination of the isotopic ratios revealed that complete interconversion of injected material was approached only by the estrone and 17[beta]-estradiol isolated from the conjugated fraction of the liver. Approximately 10% of the radioactive material recovered from the fetal liver and smaller amounts of that found in the placenta and residual fetal tissues were isolated and identified as estriol. The isetopic ratio of estriol isolated from different sources approached very closely that of conjugated estrone and 17[beta]-estradiol in the fetal liver, but was distinctly different from the isotopic ratio of free and conjugated estrone and 17[beta]-estradiol in the fetal liver, but was distinctly different from the isotopic ratio of free and conjugated estrone and 17[beta]-estradiol in all other tissues. At least 9 additional metabolites were detected in the conjugated fraction of the fetal liver. One of them was identified as 15[alpha]-hydroxy-17[beta]-estradiol, another one as 16- (or possibly 17-) epiestriol, and 2 were ring D ketolic estrogens, most probably 16[alpha]-hydroxyestrone and 16-oxo-l7[beta]-estradiol. The isotopic ratios of all identified compounds were similar to those of estrone and 17[beta]-estradiol isolated from the same fraction. It is concluded that in the feto-placental unit at midpregnancy, the liver is the main site of estrone and 17[beta]-estradiol metabolism and that this metabolism takes place predominantly in a conjugated form, most probably in form of 3-sulphates.