Effect of antiestrogen CI-628 on the morphology and 17 beta-hydroxysteroid dehydrogenase activity of mouse blastocysts in culture.
The effect of CI-628 on the morphology and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity of mouse blastocysts were compared in culture. When Day 4 mouse blastocysts were cultured in Eagle's medium containing 214 ng 3H-estradiol (E2) and CI-628 at 0, 1.5, 3, 6, 12 and 18 micrograms/ml, shedding of the zona pellucida was prevented by CI-628. The effect of CI-628 on the morphology was dose-dependent: little effects were seen at 1.5 and 3 micrograms/ml during the first 2 days, but the blastocysts became small, dense and eventually collapsed inside the zona. At 6 micrograms/ml and higher, the effect was quite pronounced. The earliest change was seen at 10 hours in 12 and 18 micrograms/ml CI-628 medium when 1/3 of the embryos became dense and smaller. All were collapsed by 22 h. CI-628 reduced the 17 beta-HSD activity slightly during the first 5 h. Nevertheless, the enzyme activity continued to increase, though at a slower rate than the control (0 microgram/ml) group, up to 22 h in the 12 and 18 micrograms/ml group, and up to 46 h in the 1.5, 3 and 6 micrograms/ml group. In the latter 3 groups, the 17 beta-HSD activity remained fairly high throughout the culture. It appears that, in comparison with the morphology, the 17 beta-HSD activity is relatively resistant to CI-628 effects. In the blastocyst homogenate, CI-628 had no effect on E2-greater than E1 conversion. It is concluded that CI-628 causes degeneration of blastocysts through mechanisms other than interfering with 17 beta-HSD activities.
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D046508:Culture Techniques; D004958:Estradiol / Q000378:metabolism; D004970:Estrone / Q000096:biosynthesis; D051379:Mice; D009594:Nitromifene / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D013997:Time Factors
D011759:Pyrrolidines; D004970:Estrone; D004958:Estradiol; D009594:Nitromifene; D015067:17-Hydroxysteroid Dehydrogenases