Add time:07/25/2019         Source:sciencedirect.com

In view of the unexpected ability of anordrin to synergize with RU 486 in terminating pregnancy, it was pertinent to examine the actions of the dihydroxylated metabolite of anordrin, Anordiol (cas 1045-29-0), alone and in combination with RU 486. Doses of RU 486 (1 mg/kg/day) and anordiol (0.6 mg/kg/day) that were ineffective when given alone terminated pregnancy with complete resorption of embryos when administered together. A smaller dose of anordiol than anordrin is required to achieve this synergistic effect with RU 486. This anordrin metabolite increased uterine weight in the ovariectomized rat similar to estradiol. The estrogenicity of anordiol in the uterine weight assay was about 1120 of that of estradiol. Anordiol does not exert antiestrogenic activity in the uterine weight assay when administered at doses that terminate pregnancy. Administration of anordiol at doses that do not terminate pregnancy resulted in a significant suppression of serum progesterone concentrations during the period of medication; these observations suggest that anordiol has an inhibitory effect on progesterone biosynthesis. When the same dose of anordiol was given concomitantly with sufficient RU 486 (e.g., 1 mg/kg/day) to terminate pregnancy, the progesterone levels were reduced to low levels throughout the experiment. These observations support the postulate that the actions of anordrin are mediated by its metabolite, anordiol. The administration of anordiol plus RU 486 results in a more dramatic change in the functional progesterone:estradiol ratio than when either agent is administered alone.

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