QUANTITATIVE ASSESSMENT OF THE DE NOVO STEROL AND STEROID SYNTHESIS IN THE HUMAN FOETO-PLACENTAL UNIT

Abstract

ABSTRACT The quantitative significance of the de novo synthesis of Δ5- and Δ4-steroids was assessed in the midgestation human foetus. Two midgestation foetuses and two complete foeto-placental units were perfused at 36°C for 120 minutes with 3.0 and 6.0 mCi of [14C] sodium acetate, respectively, and radiochemically homogeneous carbon-14 labelled steroids were isolated from the adrenals, livers and perfusates. Losses throughout the isolation procedure were monitored in all tissues of all experiments by the recovery of tritium labelled internal standards. In the four experiments, a total of 18.0 mCi of [14C] sodium acetate was perfused and a total of 0.17 μCi of pregnenolone, 2.65 μCi of pregnenolone sulphate, 1.07 μCi of dehydroepiandrosterone and 8.64 μCi of dehydroepiandrosterone sulphate were isolated. A total of 12.53 μCi were isolated in the form of these four compounds; 10.13 μCi of this was present in the perfusates. In all, 0.07% of the administered [14C]-sodium acetate was converted to the four Δ5-steroids studied and 0.048% to dehydroepiandrosterone sulphate. Progesterone was isolated from the perfusates and liver extracts, and 17α-hydroxy-progesterone, androstenedione and testosterone from the perfusates. In the four experiments, a total of 0.045 μCi of carbon-14 labelled Δ4-steroids were isolated, predominantly from the perfusates. In all, less than 0.0003% of the perfused [14C] sodium acetate was converted to Δ4-steroids. Thus, almost 300 times more Δ5- than Δ4-steroids were formed. It is concluded that the extensive de novo steroidogenetic processes taking place in the midgestation human foetus lead to the predominant formation of Δ5-steroid sulphates.