The metabolism of pregnenolone and pregnenolone sulphate was studied in incubations with minced foetal liver tissue. In most of the incubations, non-radioactive substrates were used, and the identification and quantitative determination of the metabolites formed was carried out by gasliquid chromatography and gas chromatography – mass spectrometry. Both the free and sulphated substrates were extensively metabolized by the liver preparations, and with both substrates, the same enzyme activities were observed. Furthermore, active sulphate conjugation was seen with free pregnenolone. No sulphatase activity was observed, and the direct conversion of pregnenolone sulphate to 16α-hydroxypregnenolone sulphate was demonstrated in incubations with [7-3H]pregnenolone [35S]sulphate. The highest conversion rate with both substrates, about 25 %, was for 16α-hydroxylation. Other enzyme activities detected were 20α-reduction and 3β-hydroxy-5,16-pregnadien-20-one formation. In sulphate conjugation and 16α-hydroxylation a slight decrease was observed with advancing foetal age, while in the case of 20α-reduction, somewhat higher conversion rates were observed in older foetuses. In this respect, the only significant difference between the two substrates used was the more pronounced decrease in pregnenolone sulphate 16α-hydroxylation with increasing foetal age.
This study sheds more light on the biological significance of steroid sulphates as metabolic intermediates in the human foetus and further evidence for their direct conversion into other steroid sulphates was obtained. It is suggested that the foetal liver plays an active role in such conversions.