STUDIES ON THE METABOLISM OF C-19 STEROIDS IN THE HUMAN FOETO-PLACENTAL UNIT

Abstract

ABSTRACT Four female and four male previable human foetuses (18th to 21st week of gestation) were perfused with a combination of 3H-labelled testosterone (T) and 14C-labelled androst-4-ene-3,17-dione (A) and the principal unconjugated products of dehydrogenation and reduction as well as testosterone sulphate were studied in the perfusates and various foetal tissues. 14C-labelled T derived from the metabolism of perfused A, and 3H-labelled A, originating from the perfused T, were isolated from all sources studied; as much as 2.1% of the administered A was isolated in the form of T-14C and 3.6% of the administered T was isolated as A-3H. No statistically significant sex difference was found in the interconversion of T and A; however, the extent of interconversion in one female foetus differed highly significantly (P < 0.001) from that taking place in all other foetuses. The isotopic ratios of the re-isolated A and T indicated that the interconversion was complete in the liver, partial in the gastrointestinal tract and rather limited in all other tissues. No reduction products were detected in the adrenals. From the other tissues the following unconjugated 5β-reduction products were isolated: 5β-androstane-3,17-dione from the gastrointestinal tract, liver and perfusates, 3α-hydroxy-5β-androstan-17-one (gastrointestinal tract, liver, carcass and perfusates), 5β-androstane-3α,17β-diol (liver), 17β-hydroxy-5β-androstan-3-one (liver). The following unconjugated 5α-reduction products were isolated: 5α-androstane-3,17-dione (gastrointestinal tract, liver, lungs, carcass and perfusates), 3α-hydroxy-5α-androstan-17-one (gastrointestinal tract, liver, lungs, carcass and perfusates), 3β-hydroxy-5α-androstan-17-one (lungs, carcass and perfusates), and 17β-hydroxy-5α-androstan-3-one (lungs, carcass and perfusates). The 5β-forms were predominant in the liver, their quantity exceeding that of 5α-forms by at least a factor of 100, the 5α-forms dominated the pattern in all other tissues. A sex difference in the reductive metabolism of A and T could not be ascertained. Testosterone sulphate was a major metabolite in the gastrointestinal tract and adrenals, but was not detected in the liver. On the basis of the isotopic ratios of the isolated compounds a concept is presented describing the principal pathways of the reductive metabolism of A and T in various tissues of human foetuses at midpregnancy.