Biosynthesis and Metabolism of Neutral Steroids by Human Midterm Placenta and Fetal Liver

Abstract

Radioactive progesterone, 17α-hydroxypregnenolone, androstenedione and testosterone were incubated with midterm human placenta and fetal liver. After isolation of the radioactive metabolites, purification and identification was achieved by paper and thin-layer chromatography and crystallization to constant specific activity. The analysis of the metabolites formed during incubation revealed the presence in fetal liver and midterm placenta of all enzyme systems necessary for the biosynthesis of estrone, 17β-estradiol and estriol from C₂₁- and C₁₉- steroids. Evidence for the presence of the following enzymes could be found: Δ⁵-isomerase, 3β- hydroxy dehydrogenase, 16α-hydroxylase, 17α-hydroxylase and C_17,2o-desmolase. The in vitro enzymatic activities varied quantitatively. Under the in vitro incubation conditions used, progesterone was not significantly metabolized by placenta or liver. 17α-Hydroxypregnenolone was oxidized and isomerized in high yield to 17α-hydroxyprogesterone by midterm placenta; in contradistinction, little Δ⁵-isomerase and 3β-hydroxy dehydrogenase activities were found in fetal liver. Only fetal liver showed C_17.20-desniolase activity; the yield of dehydroepiandrosterone from 17α-hydroxypregnenolone was 1.3 and 1.9%. 16α-Hydroxylation was observed for 17α-hydroxypregnenolone (or dehydroepiandrosterone), androstenedione and testosterone in both fetal liver and midterm placenta.