Antiovulatory Effect of ICI 33,828 (Methallibure) Without Affecting Prolactin Release in Normal Rats

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Abstract
Administration of a single dose of ICI 33,828 (methallibure) (5 mg/100 g) to virgin female rats on the second day of diestrus blocked the release of LH on the afternoon of proestrus. The mean values of LH (l30±ll ng) assayed by RIA decreased significantly compared to the values of control rats treated with Tween 80 (392.7 ± 56.4 ng). Methallibure did not prevent the surge of prolactin in the afternoon of the day of proestrus. The mean values between ICI 33,828-treated rats (166.8 ± 16.3 ng) and controls (198.7 ± 13.3 ng) were not significantly different, but were markedly higher than the serum prolactin levels measured on either D2 (31.0 ± 5.1 ng) or the first day of estrus (28.3 ±1.6 ng) in normal rats. In a group of methallibure-treated rats, serum prolactin levels determined on the day of estrus were significantly higher (61.0 ± 14.7 ng) than such levels in normal estrous rats. None of the rats with low levels of LH showed spontaneous ovulation on the first day of estrus. The injection of LH (10 µg/100 g) in rats previously treated with ICI 33,828, however, induced ovulation in all rats, indicating that the non-steroid inhibitor is effective by acting at hypothalamic or hypophysial levels without affecting the ovaries. It is thought that methallibure prevents ovulation by centrally blocking the release of LH. This treatment either did not affect or else stimulated prolactin release on the days of proestrus and estrus.

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