STUDIES ON OESTRIOL SYNTHESIS FROM DEHYDROEPIANDROSTERONE SULPHATE IN HUMAN PREGNANCY

Abstract

ABSTRACT The pathway of oestriol (OE3) synthesis from dehydroepiandrosterone sulphate (DHAS) was examined in human pregnancy at midterm, from both foetal and maternal compartments. In the first series of experiments, 3H-labelled DHAS and 14C-labelled oestrone sulphate (OE1S) were administered into the intact foeto-placental circulation. Oestrone (OE1), 17β-oestradiol (OE2) and OE3 formed during the 20 minutes after injection were isolated from the placenta, foetus and urine of the mother. The following observations were made: a) conversion to OE3 was greater from DHAS than OE1S, b) more OE3 was formed from DHAS than OE1 and OE2, c) the 3H/14C-ratios of the urinary OE3 were higher than those of OE1 and OE2. In the second series of experiments, three pregnant subjects were given the same combination of sulphurylated precursors via the antecubital vein, and OE1, OE2 and OE3 were isolated from their urine. In contrast to the foeto - placental studies: a) OE1S was converted to urinary OE3 in greater yield than was DHAS, b) more OE1 and OE2 were formed from DHAS than was OE3, c) the 3H/14C-ratios of the three urinary oestrogens were similar to each other. In addition, the specific activity of OE3 was lower than that of OE1 and OE2 with respect to both 3H and 14C. These results suggest that DHAS circulating within the foeto - placental compartment is converted to OE3 via both phenolic and neutral intermediates, whereas DHAS originating from the maternal circulation is converted to OE3 largely via a phenolic pathway. Approximately 80% of the OE3 formed within the foeto - placental compartment was transferred to the mother within 20 minutes. This rapid transport may explain the usefulness of urinary OE3 determinations in the assessment of foetal viability.