Acute inhibition of rat myometrial responses to oxytocin by tamoxifen stereoisomers and oestradiol.

The non-steroidal antioestrogen tamoxifen (trans-1-(4-beta-dimethylaminoethoxyphenyl)-1,2-diphenylbut- 1-ene), widely used in the treatment of breast cancer, and its oestrogenic cis-isomer rapidly inhibited contractile responses of isolated rat myometrium to supramaximal concentrations of oxytocin (1.28 X 10(-6) mol/l). Both compounds were effective at concentrations comparable with the plasma concentrations of tamoxifen reached in therapy (i.e. 5 X 10(-7) to 5 X 10(-6) mol/l). Inhibition was too rapid in onset (less than 3 min) to involve changes in RNA transcription and protein synthesis, and was not prevented or reversed by the addition of oestradiol to the bath. We conclude that the inhibition did not involve the classical oestrogen receptor pathway. Oestradiol-17 beta at concentrations above 10(-6) mol/l also inhibited the myometrium and potentiated the effects of the anti-oestrogens. Our experiments suggest that the anti-oestrogens and oestradiol act via a similar route with tamoxifen having an equilibrium affinity approximately tenfold greater than that of oestradiol.