16-dehydropregnenolone 3-sulfate, its source and metabolism in the feto-placental unit

We have investigated the serum concentration of I 6-dehydropregnenolone (3 beta-hydroxy-5,16-pregnadien-20-one) 3-sulfate (16-DHPS) in the umbilical a rtery (U.A.), umbilical vein (U.V.) and maternal vein (M.V.) to discover th e origin of 16-DHPS. Although there was no significant difference between t he levels of 16-DHPS in U.A. (18+/-15 ng/ml, mean+/-S.D., n=28) and U.V. (1 0+/-9 ng/ml, n=28), these values were significantly higher (U.A., p<0.001; U.V., p<0.001) than that in M.V. (2+/-3 ng/ml, n=28). These levels in the U .A. and U.V. did not fall in infants (30+/-18 ng/ml, n=7) during the early neonatal period (2-7 d after birth). A significant correlation between the serum levels of 16-DHPS and 16-hydroxypregnenolone (3 beta,16 alpha-dihydro xy-5-pregnen-20-one) 3-sulfate (16-OH-PregS), which may be the precursor st eroid for 16-DHPS, was observed in the U.A. (r=0.630, n=28, p<0.001), but n ot in the U.V. Moreover, this significant correlation persisted during the early neonatal period (p<0.05, r=0.842, n=7), although the neonate had been separated from the maternal milieu. These results suggest that 16-DHPS ori ginates in the fetus. To confirm the metabolic pathway of 16-DHPS (ie. pregnenolone (3 beta-hydro xy-5-pregnen-20-one) 3-sulfate (PregS)-->16-OH-PregS-->16-DHPS), we investi gated the correlation between the serum concentrations of the precursor ste roid and the product in both the U.A. and U.V, A significant correlation wa s obtained between the serum concentrations of PregS and 16-OH-PregS both i n the U.A. (p<0.001, r=0.563, n=28) and U.V. (p<0.05, r=0.476, n=27). As de scribed above, the serum levels of 16-DHPS and 16-OH-PregS only correlated significantly in the U.A. These findings support the existence of the pathw ay, PregS-->16-OH-PregS-->16-DHPS, in the fetus.