STUDIES ON THE METABOLISM OF C19 STEROIDS IN THE FOETO-PLACENTAL UNIT

Abstract

ABSTRACT Tritium labelled testosterone and carbon-14 labelled testosterone sulphate were administered into the intact foeto-placental circulation in two subjects at laparotomy and the principal conjugated metabolites present in the placenta and various foetal tissues, as well as unconjugated testosterone were isolated and identified. More than 99% of the carbon-14 labelled material recovered from the various sources was in a water-soluble (conjugated) form, whereas water-soluble metabolites accounted for some 42% of the tritium labelled material. More than 70% of the carbon-14 labelled material isolated from all tissues studied, except the liver, was present in the form of testosterone sulphate; in the liver it amounted only to some 30%. Exclusively tritium labelled unconjugated testosterone was isolated in a radiochemically homogeneous form from the placental and liver extracts, and from the combined extract of all other foetal tissues. In addition, three exclusively tritium labelled conjugated metabolites were isolated: 5α-androsterone sulphate (placenta, lungs and carcass), 5β-androsterone sulphate (placenta, liver, gastro-intestinal tract, lungs and carcass) and 3β,5β-androsterone sulphate (liver). In addition to double labelled testosterone sulphate, which was isolated from every tissue studied, double labelled 5β-dihydrotestosterone sulphate was isolated from the liver. Moreover, 5β-androstane-3α,17β-diol was isolated from the liver following solvolysis of the monosulphate fraction and 11β-hydroxytestosterone sulphate from the adrenals following solvolysis and conversion of the product to 11β-hydroxyandrostenedione. The testosterone sulphate isolated from the adrenals exhibited the highest, and that isolated from the placenta, lungs and liver the lowest tritium to carbon-14 ratio. It is concluded that significant quantities of testosterone are converted to testosterone sulphate by the foetal adrenals and that neither the foetus nor the placenta is capable of hydrolysing testosterone sulphate. The foetal metabolism of testosterone sulphate seems to be characterized by the formation of 5β-oriented conjugated reduction products in the liver and by the formation of 11β-hydroxytestosterone sulphate in the adrenals.