Formation of 15α-hydroxyestriol and 15α-hydroxyestradiol from C 19 15α-hydroxylated precursors in human pregnancy

Abstract

A mixture of 3H-15α-hydroxyandrostenedione and 14C-15α-hydroxydehydroisoandrosterone was injected intravenously into two subjects in the third trimester of pregnancy and, in a second study, directly into two fetuses in utero during transfusion for erythroblastosis fetalis. The urine was collected for 4–5 days and steroid conjugates in the urine were hydrolyzed into sulfate and glucosiduronate fractions. From the glucosiduronate fraction 15α-hydroxyestriol, 15α-hydroxyestradiol, 15α-hydroxyandrostenedione and 15α-hydroxydehydroisoandrosterone were isolated. No metabolites were identified in the sulfate fraction of the urine. A marked difference was observed in the metabolism of 15α-hydroxyandrostenedione and 15α-hydroxydehydroisoandrosterone which is dependent on the route of administration of the substrates. Both substrates were converted to 15α-hydroxyestriol and 15α-hydroxyestradiol, and the 3H/ 14C ratios and percentage conversions suggest that 15α-hydroxyandrostenedione seems to be a better precursor of the urinary 15α-hydroxylated estrogens than 15α-hydroxydehydroisoandrosterone. The 3H/ 14C ratios also suggest that 15α-hydroxydehydroisoandrosterone was converted to 15α-hydroxyestriol via 15α-hydroxyandrostenedione, and that the formation of 15α-hydroxyestradiol from 15α-hydroxydehydroisoandrosterone via 15α-hydroxyandrostenedione is a pathway of minor importance. Finally, 15α-hydroxydehydroisoandrosterone was recovered from the urine only when the precursors were injected into the maternal circulation. Also, an unknown metabolite containing only 14C was detected in the glucosiduronate fraction of the urine of each subject.