Interruption of pregnancy in rats by azastene, an inhibitor of ovarian and adrenal steroidogenesis.
Azastene (4,4,17alpha-trimethylandrost-5-eno[2,3-d]isoxazol-17-ol), when given orally to rats at a dose of 12 mg/kg once on day 10 of pregnancy, induced resorption of all fetuses and a precipitous decline of circulating progesterone levels in all test animals. The disruption of pregnancy was prevented by a single, concurrent, subcutaneous injection of progesterone (4 mg/rat). Thus, the interruption of pregnancy occurs via an acute, short-term, reversible progesterone withdrawal. The reduction of progesterone levels is brought about by competitive inhibition of ovarian 3beta-hydroxysteroid dehydrogenase activity. Despite its potency as an interceptive agent, azastene exhibited only moderate endocrine-related effects if given daily for 2 weeks to female rats at doses as high as 1000 mg/kg. Those effects were an increase in the number of vaginal estrous days and a dose-related increase in adrenal weight. The latter effect is consistent with the known adrenal inhibitory properties of this drug.
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000311:Adrenal Glands / Q000201:enzymology; D000737:Androstenols / Q000494:pharmacology*; D000818:Animals; D003345:Corticosterone / Q000097:blood; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D007555:Isoxazoles / Q000494:pharmacology; D007700:Kinetics; D010053:Ovary / Q000201:enzymology; D011247:Pregnancy / Q000187:drug effects*; D011255:Pregnancy Maintenance / Q000187:drug effects*; D011270:Pregnancy, Animal / Q000187:drug effects*; D011374:Progesterone / Q000097:blood / Q000494:pharmacology; D011555:Pseudopregnancy / Q000187:drug effects; D051381:Rats
D000737:Androstenols; D007555:Isoxazoles; C017039:azastene; D011374:Progesterone; D015096:3-Hydroxysteroid Dehydrogenases; D003345:Corticosterone