Influence of Two Nonsteroidal Antiestrogens on Vaginal Opening and PMS-Induced Ovulation in Rats

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Abstract
Oral administration of 0.5 and 1.5 mg/kg of U11555A and 0.5 mg/kg of MRL-41 induced superovulation in the PMStreated immature rat. At 0.25 mg/kg, neither compound exerted an effect on ovulation nor revealed the marked antiestrogenic action seen at higher levels as judged by uterine weight observations. As the dose of U11555A increased, the superovulatory action was diminished or eliminated. However, a significant suppression of ovulation by U11555A was never attained, even at doses of 6.0 mg/kg. On the other hand, MRL-41 significantly reduced the incidence of ovulation at 1.5 mg/kg, and caused a complete blockade of ovulation at 3.0 mg/kg. The rats that did ovulate after the 1.5 mg/kg treatment released normal numbers of ova; this suggested an “all or none” quality for the ovulation-blocking action of MRL-41. Subcutaneous administration of 0.5 mg/kg of either U11555A or MRL-41 to preweanling female rats resulted in precocious vaginal opening and ovulation. An attempt was made to relate these effects to the antiestrogenic action of these compounds. It was suggested that the compounds prevented the inhibitory influence of endogenous estrogen on luteinizing hormone secretion. (Endocrinology76: 865, 1965)

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