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

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Abstract
In four cases of therapeutic abortion by laparotomy, tracer amounts of oestrone-6,7-3H and 17β-oestradiol-16-14C were injected into the umbilical vein 20 minutes prior to the interruption of gestation, and the radioactive material recovered from the placenta and various foetal tissues was analysed. More than 92 per cent of the radioactive material recovered from the foetus, but less than 15 per cent of that present in the placenta, was in a conjugated form. Among the foetal tissues studied, the highest percentage of unconjugated (free) radioactive material (25 per cent) occurred in the adrenals. Determination of the isotopic ratios revealed that complete interconversion of injected material was approached only by the oestrone and 17β-oestradiol isolated from the conjugated fraction of the liver. Approximately 10 per cent of the radioactive material recovered from the foetal liver and smaller amounts of that found in the placenta and residual foetal tissues were isolated and identified as oestriol. The isotopic ratio of oestriol isolated from different sources approached very closely that of conjugated oestrone and 17β-oestradiol in the foetal liver, but was distinctly different from the isotopic ratio of free and conjugated oestrone and 17β-oestradiol in all other tissues. At least 9 additional metabolites were detected in the conjugated fraction of the foetal liver. One of them was identified as 15α-hydroxy-17β-oestradiol, another one as 16- (or possibly 17-) epioestriol, and two were ring D ketolic oestrogens, most probably 16α-hydroxyoestrone and 16-oxo-17β-oestradiol. The isotopie ratios of all identified compounds were similar to those of oestrone and 17β-oestradiol isolated from the same fraction. It is concluded that in the foeto-placental unit at midpregnancy, the liver is the main site of oestrone and 17β-oestradiol metabolism and that this metabolism takes place predominantly in a conjugated form, most probably in form of 3-sulphates.