Ovine fetoplacental sulfoconjugation and aromatization of dehydroepiandrosterone

Infusions of dehydroepiandrosterone (D) into pregnant ewes result in increased maternal plasma concentrations of estrone and estradiol. To investigate the role of the ovine fetoplacental unit in the conversion of D to estrogen, 6 mg D were infused into the fetal vena cava in seven chronically instrumented pregnant ewes between 124-150 days gestation. Simultaneous serial blood samples were obtained from the umbilical artery and vein, the uterine vein, and the iliac artery (representative of the uterine artery) and assayed for estrone, estradiol, D, and D sulfate. The concentration of D in the umbilical artery increased from 1.35 ± 0.35 ng/ml at time zero to 49 ± 15 ng/ml at 15 min (P < 0.025) and remained elevated at 30 min. D was unchanged in samples from the umbilical vein and uterine artery and vein. The umbilical arteriovenous difference was significant (P < 0.05). Plasma estrone and estradiol increased significantly (P < 0.05) in both fetal and maternal compartments 7.5 min after the fetal administration of D; fetal values rose higher than maternal values. Maximum concentrations of D sulfate were also achieved at 7.5 min; fetal values remained greater than maternal values (P < 0.001), and significant uterine and umbilical arteriovenous differences were observed during the first 30 min (P < 0.05). It is evident from these in vivo studies that D is extracted from umbilical cord blood by the fetal placenta, that estrogensare promptly synthesized after the infusion of D into the fetus, that sulfokinase activity in the fetoplacental unit is great, and that ovine fetoplacental aromatase activity is not rate limiting in the conversion of D to estrogen after the 124th day of pregnancy.