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

Abstract

ABSTRACT 3H-labelled androst-4-ene-3,17-dione and 14C-labelled testosterone were administered at laparotomy into the intact foeto-placental circulation and the principal metabolites present in the placenta and various foetal tissues were isolated and identified. Five subjects were investigated; all foetuses were females. Except in the liver, where there was a complete interconversion, in all tissues more testosterone was converted into androstenedione than vice versa. The following unconjugated (ether soluble) metabolites were isolated: 5β-androstane-3,17-dione from the liver, gastro-intestinal tract and residual foetal tissues; 3α-hydroxy-5β-androstan-17-one (liver, lungs, gastrointestinal tract, residual foetal tissues); 5β-androstane-3α,17β-diol (liver); 5α-androstane-3,17-dione (lungs, gastro-intestinal tract, residual foetal tissues); 3α-hydroxy-5α-androstan-17-one (lungs, gastro-intestinal tract, residual foetal tissues); 11β-hydroxyandrost-4-ene-3,17-dione (adrenals); oestrone (placenta and combined foetal tissues); 17β-oestradiol (placenta); oestriol (placenta). The following metabolites were isolated from the conjugated (water soluble) fraction of the liver: testosterone, 3α-hydroxy-5β-androstan-17-one, 3β-hydroxy-5β-androstan-17-one, 5β-androstane-3α,17β-diol, oestrone, 17β-oestradiol, oestriol. In addition, oestrone was isolated from the aqueous phase of the placentas, oestrone, 17β-oestradiol and oestriol from the aqueous phase of the combined foetal tissues, and 15α-hydroxy-oestradiol was detected and characterized in the extracts of placentas and livers. A high degree of enzymic stereospecificity in the reduction of the administered androstenedione and testosterone was observed in the various foetal tissues: 3α,5β-forms were predominant in the liver, with little, if any 3α,5α-forms present. In the lungs and residual foetal tissues, 3α,5α-products were predominant, whereas in the extracts of the gastrointestinal tract both types of reduction products were present in approximately equal amounts.