Abstract
Pregnant rhesus monkeys(120-145 days) were anesthetized with Ketamine, and a femoral maternal artery catheter and fetal umbilical artery and/or vein were cannulated by an extra-amniotic technique. Either [UL-14C] DES, [monoethyl-l-3H] DES or [6, 7, 3H] E2 in 20% ethanol was given in a maternal vein. Blood samples were collected for a 2 hr period. The maternal T½ for the 14C-DES was 35 min as compared to 100 min for 3H DES. The T½ for E2 was 45 min. Both DES and E2 appeared in the fetal circulation within 5 min and reached a maximum total radioactivity at 40-60 min. Radioactivity accumulated primarily in fetal liver, lung, intestine, uterus and brain of animals dissected immediately after the experiment. Complete analysis was performed on the total fecal and urinary products in one animal. Urinary conjugates were purified by XAD-2 and Sephadex LH-20(ME0H/ET0H 1:1). Three urinary conjugate fractions were obtained, hydrolyzed, and the aglycones identified by GC/MS to be cis/trans DES and possibly dienestrol. The principal fecal product found after extraction and LH-20 purification(benzene/MEOH 80:20) was identified thru GC/MS as DES. The fecal conjugates were chromatographically similar to the urinary conjugates. This is the first non-human primate evidence that DES crosses the placenta and accumulates in the fetus. DES pharmaco-kinetics and metabolism appear similar to natural estrogens.
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Hill, D., Helton, E., Lipe, G. et al. 300 TRANSPLACENTAL TRANSFER, METABOLISM & PHARMACOKINETICS OF DIETHYLSTILBESTROL(DES) AND ESTRADIOL 17ß(E2) IN PREGNANT RHESUS MONKEYS. Pediatr Res 12 (Suppl 4), 413 (1978). https://doi.org/10.1203/00006450-197804001-00305
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DOI: https://doi.org/10.1203/00006450-197804001-00305