ACETATE AND CHOLESTEROL METABOLISM IN THE HUMAN FOETO-PLACENTAL UNIT AT MIDGESTATION

Two complete foeto-placental units were perfused at midgestation with 5.0 mCi of uniformly labelled 14C-sodium acetate plus 5.0 mCi of cholesterol-7α-3H and two isolated foetuses were perfused with 2.5 mCi of 14C-labelled sodium acetate plus 2.5 mCi of cholesterol-7α-3H. The perfusions were carried out at 35–36°C for 90 min. The foetal adrenals, livers, testes and perfusates were analyzed and various labelled steroids were isolated in a radiochemically homogeneous form. Major quantities of 14C- and 3H-labelled pregnenolone (3β-hydroxy-pregn-5-en-20-one) and dehydroepiandrosterone (3β-hydroxy-androst-5-en-17-one) were isolated from the foetal perfusates, livers and adrenals. Minor amounts of 14C- and 3H-labelled progesterone (pregn-4-ene-3,20-dione) were isolated from the perfusates and adrenals, and 17α-hydroxy-progesterone (17α-hydroxy-pregn-4-ene-3,20-dione) and androstenedione (androst-4-ene-3,17-dione) from the perfusates. Smaller amounts of exclusively 14C-labelled androstenedione were isolated also from the adrenals. No labelled progesterone, androstenedione or testosterone (17β-hydroxy-androst-4-en-3-one) was detected in the testes. Attempts to isolate 20α-dihydroprogesterone (20α-hydroxy-pregn-4-en-3-one) or 20β-dihydroprogesterone (20β-hydroxy-pregn-4-en-3-one) from the perfusates, adrenals and livers failed. No labelled cortisol (11β,17,21-trihydroxy-pregn-4-ene-3,20-dione) or corticosterone (11β,21-dihydroxy-pregn-4-ene-3,20-dione) was detected in the adrenals, and no testosterone, oestrone (3-hydroxy-oestra-1,3,5(10)-trien-17-one) or 16α-hydroxy-dehydroepiandrosterone (3β,16α-dihydroxy-androst-5-en-17-one) in the perfusates. Pregnenolone and dehydroepiandrosterone (which were present in approximately equal amounts) accounted for as much as 95% of all steroids isolated from all sources. The bulk of these two steroids was isolated from the perfusates. The 14C/3H ratio of the pregnenolone and dehydroepiandrosterone isolated from the conjugated fraction of the perfusates was much higher than that of the unconjugated compounds. It is concluded that the midgestation human foetus is capable per se of carrying out the de novo synthesis of major quantities of pregnenolone and dehydroepiandrosterone. It is suggested that in foetal steroidogenesis acetate is utilized predominantly via a conjugated pathway and circulating cholesterol mainly via an unconjugated pathway.