EFFECT OF MIFEPRISTONE AND ANTIESTROGENS ON UTERINE PGF(2-ALPHA) AND PGE(2) CONCENTRATIONS IN OVARIECTOMIZED AND PREGNANT RATS

Four antiestrogens (anordiol, tamoxifen, RU 39411, ICI 182780) and the antiprogestin, mifepristone (RU 486), were administered to the follow ing three animal models: (1) ovariectomized rats, (2) mated rats treat ed post-coitally; and (3) pregnant rats treated post-implantation. The antiestrogens were administered alone or in combination with mifepris tone at doses effective in preventing and/or terminating pregnancy in rats. The objective of the study was to determine whether these drugs influenced uterine concentrations of prostaglandins (PGF(2 alpha) and PGE(2)). ntiestrogens administered alone to ovarectomized rats did not effect uterine PGE(2) or PGF(2 alpha) concentrations; whereas the com bination of anordiol/mifepristone increased uterne PGF(2 alpha) concen tration, resulting in an increase in the PGF(2 alpha)/PGE(2) ratio. Ma ted rats were treated post-coitally for three consecutive days with an ordiol, tamoxifen, estradiol and mifepristone alone and with the combi nation of anordiol/mifepristone and tamoxifen/mifepristone. An increas e in uterine PGF(2 alpha) concentrations and in the PGF(2 alpha)/PGE(2 ) ratio occurred only in anordiol/mifepristone treated group. A decrea se in uterine PGE(2) concentrations occurred in animals treated with a nordiol, tamoxifen and estradiol, resulting in all increase in the PGF (2 alpha)/PGE(2) ratio.