Regulation of uterine nucleolar RNA synthesis by estrogens.

Administration of estradiol to ovariectomized mature rats results in a biphasic early (4 h) and late (24 h) increase in transcriptional activity of isolated uterine nucleoli. The increased rate of nucleolar RNA synthesis is dependent upon the dose of estradiol over the range of 0.1 to 1 micrograms/animal, and exhibits hormone specificity. Administration of cycloheximide, an inhibitor of protein synthesis, prior to the administration of hormone or during the early phase of estrogen action (less than 4 h) blocks the estrogen-induced increase in uterine nucleolar transcriptional activity. Administration of cycloheximide during the later phase (greater than 8 h) of estrogen action is without effect on the estrogen-induced increase in transcriptional activity of isolated uterine nucleoli. This suggests that the longer term maintenance of the hormone-stimulated increase in nucleolar RNA synthesis is independent of continuous protein synthesis. Results indicate that the estrogen-induced accumulation and subsequent decline in uterine nuclear estradiol receptor levels is unaffected by cycloheximide treatment. Together, these results indicate the presence of the receptor-hormone complex in the nucleus is not solely responsible for the increased transcriptional activity of uterine nucleoli following in vivo hormone treatment. The early activation of uterine nucleolar RNA synthesis by estrogen seems to result from the synthesis of a short-lived protein(s) that modified RNA polymerase I and/or the nucleolar chromatin template.