Role of estrogen receptor binding and transcriptional activity in the stimulation of hyperestrogenism and nuclear bodies.

The effects of estradiol and nafoxidine on nuclear estrogen receptor binding, RNA polymerase activities, and uterine ultrastructure were studied. Animals were either injected with estradiol, implanted with estradiol/paraffin pellets, or injected with nafoxidine. Animals treated with nafoxidine or estradiol implants showed sustained long-term nuclear retention of estrogen receptor and increased nuclear RNA polymerase activities for up to 72 hr. A single injection of estradiol caused initial increases in these variables which returned to control levels by 24 hr after hormone treatment. Uterine tissue was examined by light and electron microscopy 72 hr after hormone treatments. Uteri from eith estradiol-implanted or nafoxidine-treated animals showed markedly increased hypertrophy of the luminal epithelial cells. Nuclei in sections of the uteri of these hyperestrogenized animals displayed a large number and wide array of nuclear bodies composed of a filamentous capsule and granular cores. We conclude that hyperestrogenization, a condition that eventually results in abnormal cell growth, is correlated with increased and sustained nuclear binding of the estrogen receptor, increased and sustained RNA polymerase activity, and the appearance of nuclear bodies.