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

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Abstract
3H-labelled androst-4-ene-3,17-dione and 14c-labelled testosterone were administered at laparotomy into the intact feto-placental circulation and the principal metabolites present in the placenta and various fetal tissues were isolated and identified. Five subjects were investigated; all fetuses 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: 5[beta]-androstane-3,17-dione from the liver, gastro-intestinal tract and residual fetal tissues; 3[alpha]-hydroxy-5[beta]-androstan-17-one (liver, lungs, gastro-intestinal tract, residualfetal tissues); 5[beta]-androstane-3[alpha],17[beta]-diol (liver); 5[beta]-androstane-3,17-dione (lungs, gastro-intestinal tract, residual fetal tissues); 3[beta]-hydroxy-5[alpha]-androstan-17-one (lungs, gastro-intestinal tract, residualfetal tissues); 11[beta]-hydroxyandrost-4-ene-3,17-dione (adrenals); estrone (placenta and combined fetal tissues); 17[beta]-estradiol (placenta); estriol (placenta). The following metabolites were isolated from the conjugated (water soluble) fraction of the liver: testosterone, 3[alpha]-hydroxy-5[beta]-androstan-17-one, 3[beta]- hydroxy-5[beta]-androstan-17-one, 5[beta]-androstane-3[alpha],17[beta]-diol, estrone, 17[beta]-estradiol, estriol. In addition, estrone was isolated from the aqueous phase of the placentas, estrone, 17[beta]-estradiol and estriol from the aqueous phase of the combined fetal tissues, and 15a-hydroxy-estradiol was detected and characterized in the extracts of placentas and livers. A high degree of enzymic stereospecificity in the reduction of the administered androstendione and testosterone was observed in the various fetal tissues: 3[alpha],5[beta]-forms were predominant in the liver, with little,-if any 3[alpha],5[alpha]-forms present. Li the lungs and residual fetal tissues, 3[alpha],5[alpha]-products were predominant, whereas in the extracts of the gastro-intestinal tract both types of reduction products were present in approximately equal amounts.