OBJECTIVE: Our purpose was to determine whether RU 486 (mifepristone) has direct estrogenic activity in uterine myocytes. STUDY DESIGN: Ovariectomized adult rats were treated with RU 486, and its effect on uterine oxytocin receptor concentration, as a marker of estrogenic activity, was measured. Results were compared with the induction by RU 486 of an estrogen-responsive reporter gene in a cultured Syrian hamster uterine myocyte cell line. RESULTS: Baseline oxytocin receptor concentration was 58.8 +/- 7.2 fmol/mg protein (mean +/- SEM) and increased to 227 +/- 49 fmol/mg with 17 beta-estradiol (2.5 micrograms/kg) and to 145 +/- 18 fmol/mg after RU 486 (5 mg/kg) treatment, an effect that was inhibited by the antiestrogen ICI 182,780 (1.5 mg/kg). In the cultured Syrian 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 estrogenic activity of RU 486 was dependent on the presence of both estrogen receptor and the promoter's estrogen response element. CONCLUSION: 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.
OBJECTIVE: Our purpose was to determine whether RU 486 (mifepristone) has direct estrogenic activity in uterine myocytes. STUDY DESIGN: Ovariectomized adult rats were treated with RU 486, and its effect on uterine oxytocin receptor concentration, as a marker of estrogenic activity, was measured. Results were compared with the induction by RU 486 of an estrogen-responsive reporter gene in a cultured Syrian hamster uterine myocyte cell line. RESULTS: Baseline oxytocin receptor concentration was 58.8 +/- 7.2 fmol/mg protein (mean +/- SEM) and increased to 227 +/- 49 fmol/mg with 17 beta-estradiol (2.5 micrograms/kg) and to 145 +/- 18 fmol/mg after RU 486 (5 mg/kg) treatment, an effect that was inhibited by the antiestrogen ICI 182,780 (1.5 mg/kg). In the cultured Syrian 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 estrogenic activity of RU 486 was dependent on the presence of both estrogen receptor and the promoter's estrogen response element. CONCLUSION: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.