Dissociation of estrogen-induced uterine growth and ornithine decarboxylase activity in the postnatal rat.
Estrogens 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 EE2 were 2.7% and 4.9% of that for E2 binding to AFP, determined in a batch Sephadex equilibrium binding assay. On days 1-5, DES and EE2 were about 80-fold more potent than E2 in increasing uterine weight. As AFP levels fell, potency differences between E2 and 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 E2 levels 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 intracellular events.
D000375:Aging; D000818:Animals; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000097:blood; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding; D051381:Rats; D014599:Uterus / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development*; D000509:alpha-Fetoproteins / Q000378:metabolism
D004967:Estrogens; D000509:alpha-Fetoproteins; D004997:Ethinyl Estradiol; D004958:Estradiol; D004054:Diethylstilbestrol; D009955:Ornithine Decarboxylase