Estrogen-induced changes in rRNA accumulation and RNA polymerase I activity in the rat pituitary: correlation with pituitary tumor susceptibility.

Chronic treatment with the synthetic estrogen diethylstilbestrol induces pituitary tumors in rats and the susceptibility to such tumors is highly strain dependent. The Fischer 344 (F344) strain, which is particularly susceptible, develops pituitary tumors after 30-55 days of estrogen treatment. In contrast, the Sprague-Dawley (SD) strain is relatively resistant to such tumors. DES implants (5 mg) were placed in 21-day-old male rats over a 10-day period and changes in their testes and pituitaries were monitored. Both F344 and SD strains responded similarly by exhibiting a measurable decrease in testes weight to one-third that of controls on day 10. In F344 rats, DNA synthesis in the pituitary increased to 228% as compared with controls after 3 days of DES treatment and remained high on days 7 and 10. In SD rats, DNA synthesis increased to only 150% of that exhibited by controls on day 3 and started to decline on day 7. Surprisingly, total RNA accumulation also responded to DES differentially between these two strains. In F344 rats, the RNA level was 250% as compared with that of controls after 3 days of DES treatment and continued to increase gradually on days 7 and 10. The RNA level in the SD strain increased only slightly from the same DES treatment. A nuclear run-on assay showed elevated pituitary transcription of ribosomal DNA in the F344 rats after 3 days of estrogen administration. The enzymatic activity of pituitary RNA polymerase I, the enzyme responsible for initiating rRNA synthesis, increased twofold in F344 rats when measured after 3 days of estrogen treatment whereas no increase was observed in the SD rats. These results suggest that estrogen-induced changes in the accumulation of rRNA occur at a very early stage in tumorigenesis, prior to any visible tumor growth in the rat pituitary.