METABOLISM OF OESTRONE SULPHATE BY THE PREVIABLE HUMAN FOETUS

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Abstract
Two previable fetuses (20th week of gestation) were perfused with a combination of estrone-6,7-H3 and estrone-16-C14 sulphate. Approximately 80% of the perfused radioactive material was recovered from the various fetal tissues and perfusates in both experiments. In contrast to the H3-labelled material, very little C14-labelled material was recovered from the various fetal tissues, except from the liver, which showed an approximately equal uptake of the 2 isotopes. Thirty-six per cent of the H3- and as much as 68% of the C14-labelled material administered was recovered from the perfusate. No C14-labelled material was detected in any of the extracts of the fetal tissues and perfusates as unconjugated (free) material. No estriol or 15[alpha]-17[beta]-estradiol could be isolated from the extracts of any of the fetal tissues, except from the liver, where these compounds were present mainly, if not exclusively, as conjugated material. Approximately 10% of the H3 - and C14-iabelled conjugated material recovered from the liver was isolated as estriol and some 5% of it as 15[alpha][long dash]hydroxy-17[beta]-estradiol. The isotopic ratio H3/C14) of these compounds was lower than that of estrone and 17[beta]-estradiol isolated from the same fraction. Very little, if any estriol or 15[alpha]-hydroxy-17[beta]-estradiol was detected in the extracts of perfusates. On the other hand, large quantities of some ketonic precursors of estriol, 15[alpha]-hydroxy-17[beta]-estradiol and of additional highly polar metabolites were present. Following reduction, estriol was isolated and 15[alpha]-hydroxy-17[beta]-estradiol identified in the extracts of perfusates. The isotopic ratio of these 2 compounds was similar to the isotopic ratio of those found in the liver. It is concluded that: the midterm human fetus is not capable of hydrolysing estrogen sulphates; in the fetal organism estrone sulphate is mostly taken up by the fetal liver, where the extent of its uptake and metabolism is at least as great as that of estrone; 15[alpha]- and 16[alpha]-hydroxylation of estrone takes place mainly, if not exclusively, in the fetal liver and predominantly in form of conjugated material, the 15[alpha]- and 16[alpha]-hydroxylated conjugated metabolites formed from estrone sulphate are released by the fetal liver into the fetoplacental circulation mainly as ketonic intermediates, rather than completely reduced compounds.