Estrogen-induced transcription of the progesterone receptor gene does not parallel estrogen receptor occupancy

The activation of the silent endogenous progesterone receptor (PR) gene by 17-beta-estradiol (E(2)) in cells stably transfected with estrogen receptor (ER) was used as a model system to study the mechanism of E(2)-induced transcription, The time course of E(2)-induced PR transcription rate was determined by nuclear run-on assays. No marked effect on specific PR gene transcription rates was detected at 0 and 1 h of E(2) treatment. After 3 h of E(2) treatment, the PR mRNA synthesis rate increased 2.0- +/- 0.2-fold and continued to increase to 3.5- +/- 0.4-fold by 24 h as compared with 0 h. The transcription rate increase was followed by PR mRNA accumulation. No PR mRNA was detectable at 0, 1, and 3 h of E(2) treatment, PR mRNA accumulation was detected at 6 h of E(2) treatment and continued to accumulate until 18 h, the longest time point examined. Interestingly, this slow and gradual transcription rate increase of the endogenous PR gene did not parallel binding of E(2) to ER, which was maximized within 30 min, Furthermore, the E(2)-ER level was down-regulated to 15% at 3 h as compared with 30 min of E(2) treatment and remained low at 24 h of E(2) exposure, These paradoxical observations indicate that E(2)-induced transcription activation is more complicated than just an association of the occupied ER with the transcription machinery.