ESTROGENIC ACTIVITY OF RU-486 (MIFEPRISTONE) IN RAT UTERUS AND CULTURED UTERINE MYOCYTES

OBJECTIVE: Our purpose was to determine whether RU 486 (mifepristone) has direct estrogenic activity in uterine myocytes. STUDY DESIGN: Ovar iectomized adult rats were treated with RU 486, and its effect on uter ine oxytocin receptor concentration, as a marker of estrogenic activit y, was measured. Results were compared with the induction by RU 486 of an estrogen-responsive reporter gene in a cultured Syrian hamster ute rine myocyte cell line. RESULTS: Baseline oxytocin receptor concentrat ion was 58.8 +/- 7.2 fmol/mg protein (mean +/- SEM) and increased to 2 27 +/- 49 fmol/mg with 17 beta-estradiol (2.5 mu g/kg) and to 145 +/- 18 fmol/mg after RU 486 (5 mg/kg) treatment, an effect that was inhibi ted by the antiestrogen ICI 182,780 (1.5 mg/kg). In the cultured Syria n hamster uterine myocyte cell line cells RU 486 (10(-6) mol/L) caused a 2.17 +/- 0.17-fold increase in the expression of the reporter gene versus 113.0 +/- 7.4-fold with 17 beta-estradiol (10(-8) mol/L). The e strogenic activity of RU 486 was dependent on the presence of both est rogen receptor and the promoter's estrogen response element. CONCLUSIO N: RU 486 has a weak estrogen-like activity in uterine myocytes. This activity may partly explain the therapeutic effects of RU 486 on this target organ.