Pregnanolones, pregnenolone and progesterone in the human feto-placental circulation at term of pregnancy

Abstract Epimeric 3α/β-hydroxy-5α/β-pregnan-20-ones and 3β-hydroxy-5-pregnen-20-one were determined in maternal and fetal plasma at term of pregnancy using gas chromatography and electron capture detection. Fifteen sets of plasma samples (maternal vein, umbilical vein and -arteries) were obtained at cesarean section. In fetal and in maternal plasma the metabolites were present mainly in sulfoconjugated form (range 0–1.2 μg/ml). The free steroids, especially in fetal plasma (range 0–170 ng/ml), were sometimes undetectable. 3α-hydroxy-5α-pregnan-20-one and 3β-hydroxy-5α-pregnan-20-one levels were similar in fetal arteries, umbilical vein and maternal vein. A significant arterio-venous difference was observed only for 3α-sulfoxy-5β-pregnan-20-one in cord plasma with higher concentrations in fetal arterial plasma. Pregnenolone sulfate levels in the fetoplacental circulation were higher in fetal arterial plasma (20–2490 ng/ml) than in umbilical vein plasma (0–160 ng/ml). These results show that ring-A-saturated metabolites of progesterone are present in the fetoplacental circulation at concentrations sometimes higher than those of the parent steroid. From the calculation of arterio-venous differences in cord blood it can be concluded that 3α-hydroxy-5β-pregnan-20-one seems to be eliminated more effectively from the fetal compartment than are the 5α-epimers. The possibility that saturated metabolites in the fetoplacental system are derived not only from progesterone but are also formed directly from pregnenolone is discussed.