METABOLISM OF OESTRONE SULPHATE BY THE PREVIABLE HUMAN FOETUS

Abstract

ABSTRACT Two previable foetuses (20th week of gestation) were perfused with a combination of oestrone-6,7-3H and oestrone-16-14C sulphate. Approximately 80 per cent of the perfused radioactive material was recovered from the various foetal tissues and perfusates in both experiments. In contrast to the 3H-labelled material, very little 14C-labelled material was recovered from the various foetal tissues, except from the liver, which showed an approximately equal uptake of the two isotopes. Thirty-six per cent of the 3H- and as much as 68 per cent of the 14C-labelled material administered was recovered from the perfusate. No 14C-labelled material was detected in any of the extracts of the foetal tissues and perfusates as unconjugated (free) material. No oestriol or 15α-hydroxy-17β-oestradiol could be isolated from the extracts of any of the foetal tissues, except from the liver, where these compounds were present mainly, if not exclusively, as conjugated material. Approximately 10 per cent of the 3H- and 14C-labelled conjugated material recovered from the liver was isolated as oestriol and some 5 per cent of it as 15α-hydroxy-17β-oestradiol. The isotopic ratio (3H/14C) of these compounds was lower than that of oestrone and 17β-oestradiol isolated from the same fraction. Very little, if any oestriol or 15α-hydroxy-17β-oestradiol was detected in the extracts of perfusates. On the other hand, large quantities of some ketonic precursors of oestriol, 15α-hydroxy-17β-oestradiol and of additional highly polar metabolites were present. Following reduction, oestriol was isolated and 15α-hydroxy-17β-oestradiol identified in the extracts of perfusates. The isotopie ratio of these two compounds was similar to the isotopie ratio of those found in the liver. It is concluded that the midterm human foetus is not capable of hydrolysing oestrogen sulphates in the foetal organism oestrone sulphate is mostly taken up by the foetal liver, where the extent of its uptake and metabolism is at least as great as that of oestrone 15α- and 16α-hydroxylation of oestrone takes place mainly, if not exclusively, in the foetal liver and predominantly in form of conjugated material the 15α- and 16α-hydroxylated conjugated metabolites formed from oestrone sulphate are released by the foetal liver into the foetoplacental circulation mainly as ketonic intermediates, rather than completely reduced compounds.