Pregnenolone and pregnenolone sulfate metabolism in vivo and uterine extraction at midgestation.

Abstract

The in vivo metabolism and uterine extraction of pregnenolone and pregnenolone sulfate have been studied during a continuous infusion of the radioactive steroids in 5 women at midgestation. The blood metabolic clearance rates of pregnenolone and pregnenolone sulfate were 3310 ± 435 (se) 1/day and 272 ± 27 (se) 1/day. The transfer constant [ρ] of pregnenolone to pregnenolone sulfate was 0.46 ± 0.07 (se) and of pregnenolone sulfate to pregnenolone 0.10 ± 0.07 (se). The calculated transfer constants of pregnenolone and pregnenolone sulfate to progesterone were 0.04 ± 0.02 (se) and 0.02 ± 0.005 (se), respectively, and to 20α-hydroxypregn-4-en-3-one, 0.02 ± 0.004 (se) and 0.02 ± 0.006 (se). The concentration of radioactive pregnenolone sulfate was not significantly different, but the concentration of radioactive pregnenolone was significantly lower in the uterine veins compared to the antecubital vein in the isotopic steady state. The uterine extraction of pregnenolone in the anesthetized woman at midgestation was 10.1 ± 3.7 (se) %. The transuterine conversion of pregnenolone to progesterone was 0.17 ± 0.04 (se) and it was calculated that a significant portion of the conversion of pregnenolone to progesterone was occurring at sites other than the pregnant uterus. Radioactive pregnenolone sulfate could not be isolated from the umbilical vein, and it is concluded that circulating maternal pregnenolone sulfate is not a source for pregnenolone sulfate in the fetus at midgestation. Radioactive progesterone was present in the umbilical vein in higher concentrations than in the maternal blood. From the difference in the concentration of radioactive progesterone in the umbilical vein and artery a fetal extraction of progesterone of approximately 50% was estimated.