Biological activities of chlormadinone acetate. II. Effects on pregnancy, fetal development and parturition in rats

Abstract

Chlormadinone acetate (CMA) was administered subcutaneously or orally to the pregnant rats at various gestational stages, and its effects on the course of pregnancy, fetal development and parturition were studied in comparison with those of certain other steroids. The day finding sperm or plug in the vaginal smear was designated as the 1st day of pregnancy. Pregnant rats were isolated from each other, fed with ordinary rat chow, and given tap water ad libitum. The results are summarized as follows : (1) CMA is as effective as progesterone at a daily dose of 8 mg in maintaining pregnancy of the rat ovariectomized in early pregnancy. Medroxyprogesterone acetate (MAP) is about twice as active as CMA, but norethisterone is inactive in this assay.(2) Neither progesterone nor CMA inhibits ova-implantation in rats when administered subcutaneously at a daily dose of 1 mg from the first to the sixth day of gestation. MAP produces weak inhibition and norethisterone produces complete inhibition at the same dosage.(3) Oral administration of CMA produces neither fetal resorption, fetal malformation, fetal masculinization nor feminization in anogenital distance at a daily dose of 8 mg. On the contrary, norethisterone administered subcutaneously at the stage of gestation produces fetal resorption at a daily dose of 2 mg.(4) When administered subcutaneously at the later stage of gestation, CMA produces feminization of male litters with no masculinization of female litters at a daily dose of 8 mg. MAP induces sexual neutralization, both masculinization and feminization, while norethisterone causes only masculinization of female litters.(5) Parturition is delayed by the subcutaneous treatments of all progestins from twentieth day of gestation with a daily dose of 1 mg for CMA, 0.4 mg for progesterone and norethisterone, and 0.04 mg for MAP.Considering the above results, CMA, like progesterone, is characterized as a pregnancy supporting steroid, “gestagen”, whereas norethisterone is considered as a pregnancy blocking steroid, “claudogen”