Direct Mitogenic Effect of Estrogen on the Prepuberal Rat Uterus: Studies on Isolated Nuclei*

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Abstract
Isolated uterine nuclei incorporate [3H]deoxythymidine-5''-triphosphate into acid-precipitable material for 60 min. The rate and extent of incorporation is markedly enhanced by prior treatment of rats with estradiol-17.beta.. This stimulation is dose dependent and follows a time course which parallels that which is observed in intact uteri. The maximum response occurs 24 h after an injection of estradiol-17.beta. when the DNA synthesis rate has shown an 8.5 .+-. 0.9-fold average stimulation over 34 experiments. When a small dose of estradiol-17.beta. was injected directly into 1 uterine horn, DNA synthesis was stimulated in nuclei isolated from that horn but not in nuclei from the vehicle-injected contralateral horn. The mitogenic effect of estrogen is direct and not mediated by systemic factors. As shown by diethylaminoethyl-cellulose chromatography and inhibition studies with N-ethylmaleimide and 2'':3''-dioxythymidine-5''-triphosphate, the uterine nuclei contain both DNA polymerases .alpha. and .beta.; however, .alpha.-polymerase alone appears to be responsible for the estrogen-stimulated DNA synthesis. When soluble DNA polymerase .alpha.-activity and endogenous DNA synthesis rates were simultaneously measured, both were initially stimulated between 12 and 15 h after an injection of estradiol-17.beta.. Because the fold-stimulation of .alpha.-polymerase activity was only half that of DNA synthesis, it appears that DNA synthesis is not merely a simple function of polymerase activity.