Effects of Ergocornine on the Mechanism of Gestation and on Fetal Morphology in the Rat

The mode of action of ergocornine was investigated by means of 2 different experimental procedures. A first group of animals was composed of hypophysectomized female rats bearing a pituitary under the kidney capsule, and daily injected with high dosages (15 μg) of estradiol. Whereas under these conditions the diestrus was maintained and the vagina had a gravid aspect, a single injection of ergocornine methanesulfonate (1 mg) restored vaginal cornification within a few days; it persisted as long as estradiol was injected. This suggests that ergocornine has been able to inhibit the elaboiation of pituitary prolactin, even suppressing the influence of estrogen on this process. In the second experimental group, ergocornine was given to pregnant rats. When it was administered on the 5th day at small dosages (0.18–0.3 mg), it did not interfere with implantation, which more particularly was neither delayed nor asynchronous. Dosages from 0.35 to 1.0 mg, although they did not always inhibit implantation, were very deleterious for the maintenance of pregnancy. However, these treatments did not significantly increase the incidence of embryopathies. The administration of 1 mg of ergocornine on the 8th day seriously disturbed pregnancy and, moreover, induced a very significant increase in fetal malformations. When the same treatment was given on the 12th day, it had no detrimental effect on pregnancy. A progesterone treatment (5 mg daily), beginning on the day when ergocornine was given, allowed pregnancy to be almost perfectly maintained. Fetal malformations decreased when the supplementary progesterone treatment was started on the 8th day. In females that maintained their gestation in spite of the administration of ergocornine, the ovaries contained corpora lutea formed of large luteal cells, similar to those seen in normal pregnancy corpora lutea. The significance of this finding is discussed. It was concluded that: 1) Whereas ergocornine inhibits the secretion of pituitary luteotrophin, it does not affect that of placental prolactin; 2) corpora lutea having regressed under the action of ergocornine become insensitive to pituitary prolactin but can be reactivated by placental prolactin; 3) the teratogenic activity of ergocornine seems to be mediated by the progesterone deficiency that it induces. (Endocrinology 84: 315, 1969)