The ontogeny of estrogen responsiveness reexamined: the differential effectiveness of diethylstilbestrol and estradiol on uterine deoxyribonucleic acid synthesis in neonatal rats.

Previous reports have indicated that 17 beta-estradiol is unable to stimulate DNA synthesis in the neonatal rat uterus. Possible causes for this unresponsiveness that have been suggested include the ontogenic acquisition of late responses to estrogen and the sequestering of injected estradiol by the higher concentration of serum alpha-fetoprotein. To test these hypotheses we have examined the mitogenic potency of diethylstilbestrol (DES), a nonsteroidal estrogen which has a lower affinity for alpha-fetoprotein. Our results reveal that 1.0 microgram DES administered in a single injection can stimulate DNA synthesis 24 h later in 5-day-old rats, the youngest tested. By comparison, a single injection of 1.0 microgram estradiol did not stimulate DNA synthesis until rats reached an age of 10-15 days. Higher doses of estradiol administered in a single injection stimulated DNA synthesis in neonates but to a lesser extent than DES. The potency of estradiol relative to DES increased with age up to 28 days, at which time they were equipotent. The magnitude of the stimulation of DNA synthesis increased with age even with DES because control levels of DNA synthesis are high in young rats and decreased as the rats matured. These results indicate that uterine cells of neonatal rats have no inherent inability to synthesize DNA in response to estrogen and are consistent with the hypothesis that serum alpha-fetoprotein is responsible for the decreased potency of estradiol.