Implantation delay and anti-deciduogenic activity in the rat by the anti-androgen, hydroxyflutamide.
Studies were undertaken to determine whether the anti-androgen, hydroxyflutamide, has anti-progestagenic activity by using implantation, maintenance of pregnancy, and decidualization as end points. Prepubertal rats were induced to ovulate with the injection of 4 IU pregnant mare's serum gonadotropin and allowed to mate. Mated females were assigned randomly to various treatment groups. Beginning at 0800 h on Day 4 of pregnancy and at 12-h intervals thereafter, rats received a series of 6 s.c. injections of 5 mg hydroxyflutamide in oil, or oil only. Localized changes in endometrial vascular permeability, indicative of implantation, were assessed on Days 6 and 8 of pregnancy, after an injection of Evans blue dye. By Day 6, implantation has been initiated in the vehicle-treated rats, but not in hydroxyflutamide-treated rats. Hydroxyflutamide treatment was terminated on Day 6, and implantation was initiated by Day 8. The weights of uterine dye sites in hydroxyflutamide-treated rats on Day 8 were similar to those in vehicle-treated rats on Day 6. The number of fetuses and placentae were similar in all groups on Day 19. The weights of fetuses in both hydroxyflutamide-treated and hydroxyflutamide + progesterone-treated rats were similar and significantly lower than those in control rats. Although there were no significant differences between vehicle-treated or hydroxyflutamide-treated rats in the proportion of rats delivering and litter size, the hydroxyflutamide-treated rats delivered pups a mean of one day later than did the controls. Endometrial decidualization in ovariectomized, steroid-treated rats, following artificial stimuli, was significantly suppressed in hydroxyflutamide-treated rats compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Chandrasekhar
Y
Y
Department of Physiology, University of Western Ontario, London, Canada.
Armstrong
D T
DT
Kennedy
T G
TG
D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D003656:Decidua / Q000187:drug effects*; D010064:Embryo Implantation / Q000187:drug effects*; D010065:Embryo Implantation, Delayed / Q000187:drug effects*; D005260:Female; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D000813:Anilides; C014290:hydroxyflutamide; D005485:Flutamide