Transplacental estrogen responses in the fetal rat: increased uterine weight and ornithine decarboxylase activity.
The synthetic estrogens, diethylstilbestrol (DES) and ethynylestradiol (EE2), are more potent than 17 beta-estradiol (E2) in inducing uterine weight gain in the neonatal rat, due to the binding of E2 to serum alpha-fetoprotein (AFP). However, all three hormones are equipotent in inducing neonatal uterine ornithine decarboxylase (ODC) activity. The present study assessed estrogen potency in fetal rats. Pregnant CD rats were injected sc daily on gestation days (GD) 16-20 with DES, EE2, or E2 in sesame oil. Both DES and EE2, but not E2, significantly increased uterine weight at birth, to more than twice that of controls. In addition, implants which continuously release E2 only slightly increased uterine weight at birth. Alternatively, dams were given a single estrogen injection on GD 20 and were sacrificed at various times after injection. Peak fetal uterine ODC activity occurred at 6-8 hours after maternal injection for all three estrogens. E2 had a relative potency about tenfold less than either DES or EE2 in stimulating fetal ODC activity, in contrast to equal potencies of the three estrogens in the postnatal rat uterus. Similar patterns were found following direct fetal injection with E2 or DES. In summary, these data demonstrate a transplacental induction of fetal uterine ODC activity and uterine weight gain by both DES and EE2. In addition, the lack of correlation between these endpoints in response to E2 suggests that they may be useful as selective indicators of potential toxicity of both natural and synthetic estrogens.
Harmon
J R
JR
Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079.
Branham
W S
WS
Sheehan
D M
DM
D000818:Animals; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects; D007260:Infusion Pumps; D008431:Maternal-Fetal Exchange; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D013723:Teratogens; D014599:Uterus / Q000002:abnormalities / Q000187:drug effects* / Q000201:enzymology
D004343:Drug Implants; D013723:Teratogens; D004997:Ethinyl Estradiol; D004958:Estradiol; D004054:Diethylstilbestrol; D009955:Ornithine Decarboxylase