Effects of prostaglandin F2 alpha and an antiprogestational steroid, RMI 12,936, on rat pregnancy.
The abortifacient efficacy of RMI 12,936 (17 beta-hydroxy-7 alpha-methyl androst-5-en-3-one), a synthetic steroid, alone or in combination with prostaglandin-f2 alpha (PGF2 alpha), was studied in the rat. Administration on day-8 of pregnancy (PD-8) of 0.25 mg RMI 12,936/rat neither altered the progesterone (delta 4P) levels, the relative ovarian weight (ROW) nor terminated pregnancy. Doses of 2.0, 1.0 or 0.5 mg RMI 12,936/rat, when given on PD-8, terminated pregnancy in 100% of the animals. Highly significant increases in ROW and serum alpha 4P level were recorded on PD-14. However, delta 4P/20 alpha-dihydroprogesterone ratio remained unaltered. These results suggest that RMI 12,936 increased luteal activity which contributed to the enhanced serum delta 4P levels and ROW. Bilateral insertion of Silastic-PVP tubes containing 75 micrograms PGF2 alpha/tube into each uterine horn on PD-10 did not disturb pregnancy, whereas similar tubes given on PD-10 to rats treated with 1.0 mg RMI 12,936 on PD-8 expelled the embryos and placental tissue on PD-11. This phenomenon was attributed to a decreased serum delta 4P caused by PGF2 alpha, allowing the expulsion of uterine contents. A time lapse of 17--35 days was needed for the rats to regain fertility in terms of normal gestation period and offsprings. Although expulsion of conceptus was facilitated by PGF2 alpha in the RMI 12,936 treated rats, PGF2 alpha treatment did not alter the time lapse between RMI 12,936 treatment and subsequent conception. It is concluded that RMI 12,936 is feto-toxic; it possesses high contraceptive activity and its abortifacient efficacy can be improved by PGF2 alpha.
D000028:Abortion, Induced; D000737:Androstenols / Q000494:pharmacology*; D000818:Animals; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000097:blood; D005260:Female; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects; D010920:Placenta / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011284:Pregnenolone / Q000097:blood; D011374:Progesterone / Q000097:blood; D011460:Prostaglandins F / Q000494:pharmacology*; D051381:Rats; D012098:Reproduction / Q000187:drug effects; D013739:Testosterone / Q000097:blood
D000737:Androstenols; D011460:Prostaglandins F; D004970:Estrone; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; C010528:17-beta-hydroxy-7 alpha-methyl-androst-5-en-3-one; D011284:Pregnenolone