STUDIES ON THE AROMATISATION OF NEUTRAL STEROIDS IN PREGNANT WOMEN

Abstract
In 15 cases of therapeutic abortion by laparotomy the placenta was disconnected from the fetus and perfused in situ with tracer amounts of radioactive dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), androst-4-ene-3,17-dione (A), testosterone (T) and 17[beta]-estradiol (OE2). Analysis of the placentas, perfusates and urine samples revealed an extensive aromatisation of DHA, A and T; more than 70% of the radioactive material recovered was phenolic, and at least 80% of this phenolic material was identified as estrone (OE1), 17[beta]-estradiol (OE2) and estriol (OE3), the latter being detected only in the urine. Comparative studies indicated that A and T were aromatised somewhat better than DHA and that all 3 unconjugated steroids were aromatised to a much greater extent than DHAS. Radioactive OE1 and OE2 were isolated and identified in the placentas and perfusates, but no OE3, epimeric estriols, or ring D ketols could be detected in these sources, not even when human chorionic gonadotrophin (HCG) was added to the blood prior to perfusion. Lack of placental 16-hydroxylation was also apparent when OE2 was perfused. Regardless of the precursor perfused, there was 3 times more OE2 than OE1 in the placenta and 3 times more OE1 than OE2 in the perfusate. This was also the case following perfusion with OE2. The results are interpreted as suggesting the existence in the pregnant human of a placental "barrier" limiting the passage of circulating androgen. The barrier consists of limited ability to transfer directly DHAS and an enzymic mechanism resulting in the rapid and extensive aromatisation of the important androgens DHA, A and T.