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

Abstract

ABSTRACT In order to assess the quantitative significance of the de novo cholesterol synthesis in the foeto-placental unit at midgestation, two midgestation foetuses and two complete foeto-placental units were perfused with [14C]-sodium acetate immediately following their removal at laparotomy. The perfusions were carried out at 36°C for 120 min administering 3.0 and 6.0 mCi of [14C] sodium acetate, respectively. The amount of [14C]-cholesterol formed was estimated on the basis of the recovery of [7α-3H]-cholesterol internal standard present in the radiochemically homogeneous cholesterol isolated from the various tissues. The cholesterol isolated from the placentas was devoid of any [14C] label. On the other hand, [14C] cholesterol was isolated from all perfusates, as well as from all foetal tissues studied, including the adrenals, livers, testicles, brains and residual foetal tissues. The average quantity of radiochemically homogeneous [14C] cholesterol formed by the four foetuses corresponded to 0.68% of the radioactive material perfused: 0.45% was isolated from the liver, 0.13% from the adrenals, 0.01% from the testicles and 0.08% from the perfusates. Cholesterol sulphate was also isolated from the extracts of adrenals, livers and perfusates. The quantity of [14C] cholesterol sulphate formed was much less than that of [14C] cholesterol; following correction for procedural losses, the total amount of [14C] cholesterol sulphate isolated did not exceed 0.01% of the perfused material. It is concluded that the midgestation human foetus synthesizes large quantities of cholesterol, utilizing small molecular material such as sodium acetate as a precursor and that part of the cholesterol synthesized by the foetus is secreted to the placenta.