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.


METHODS
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.


CONCLUSIONS
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.
Dibbs
K I
KI
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Sadovsky
Y
Y
Li
X J
XJ
Koide
S S
SS
Adler
S
S
Fuchs
A R
AR
D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D017930:Genes, Reporter; D008647:Mesocricetus; D015735:Mifepristone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000032:analysis; D014162:Transfection; D014599:Uterus / Q000166:cytology / Q000187:drug effects*
D004965:Estrogen Antagonists; D018045:Receptors, Oxytocin; D000077267:Fulvestrant; D015735:Mifepristone; D004958:Estradiol