Genistein and daidzein modulate in vitro rat uterine contractile activity

The present study investigated the effect of genistein. daidzein and estrad iol on in vitro rat uterine responsiveness to oxytocin (OT) and PGF(2)alpha or luprostiol (L). In a first experiment, animals were either sham-operate d (SH; n = 5). or ovariectomized (OVX; n = 20) and orally treated for three months with either genistein (G: n = 5; 10 mug/g BW/d) or daidzein (D; n = 5; 10 mug/g BW/d) or 17 alpha -ethinylestradiol (E; n = 5; 23 mug/kg BW/d) or untreated (OVX; n = 5). At necropsy, the basal uterine tension was lowe r in OVX, G and D than in SH, the highest value being measured in E. Oxytoc in (10(-12); 10(-11) M) or PGF(2)alpha (10(-12); 10(-9) M) induced an incre ase in SH, but not in OVX, E and G. In D, only the highest doses were effic ient. In a second experiment, 20 intact animals were s.c. injected with eit her genistein (G; n = 5; 10 mug/g BW) or daidzein (D; n = 5; 10 mug/g BW) o r estradiol benzoate (E; n = 5; 23 mug/kg BW) or vehicle (C: controls; n = 5), and killed 24 h later. In C and E, OT (10(-15) to 10(-10) M) or L (10(- 12) to 10(-7) M) stimulated uterine contractile activity in a dose-dependen t manner until a maximal level. On the opposite, in G and D, contractile ag ents (except the highest luprostiol doses) did not stimulate myometrium con tractions. Moreover, radioligand binding assays showed that genistein or da idzein inhibited the specific binding of [H-3] estradiol to the calf uterus estrogen receptor (ER). Therefore, it could be postulated that both genist ein and daidzein might bind to the rat uterus ER, inducing either anti-estr ogenic or very weak estrogenic effects (depending on the experimental condi tions) on in vitro uterine responsiveness to OT and PGF(2)alpha or luprosti ol. (C) 2001 Elsevier Science Ltd. All rights reserved.