AbstractEstrogens are teratogens and developmental carcinogens in several species. We have used uterine growth to quantitate the potency of three estrogens estradiol (E2), diethylstilbestrol (DES), ethynylestradiol (EE2) during four postnatal periods (days 1–5, 10–14, 20–24, and 60–64) in the rat. Alphafetoprotein (AFP), present at high levels in neonatal serum, is thought to regulate estrogen bioavailability. Association constants for DES and EE2were 2.7 and 4.9 of that for E2binding to AFP, determined in a batch Sephadex equilibrium binding assay. On days 1–5, DES and EE2were about 80‐fold more potent than E2in increasing uterine weight. As AFP levels fell, potency differences between E2and the synthetic estrogens decreased. In the adult, which essentially lacks AFP, the three estrogens were nearly equipotent. These data are consistent with AFP regulation of estrogen potency. On days 10–14, uterine growth was less sensitive than at other ages to all three estrogens, perhaps related to uterine differentiation and/or the high endogenous serum E2levels reported at this age.However, when we examined another uterine estrogen response, ornithine decarboxylase (ODC) induction at 6 h following estrogen injection, all three hormones were about equipotent in both neonatal and adult animals. This apparently AFP‐independent event shows dissociation of ODC induction and uterine growth, which could be due to separate mechanisms for hormone entry to target tissue or subsequent intra
展开▼
