Biology of Reproduction, Vol 18, 99-104, Copyright © 1978 by Society for the Study of Reproduction

Inhibitory Effects of RU 16117, a Potent Estrogen Antagonist, on the Estrous Cycle in the Rat

¹ Medical Research Council Group in Molecular Endocrinology, Le Centre Hospitalier de l'Universite Laval, Quebec, G1V 4G2, Canada, and Centre de Recherches, Roussel-UCLAF, Romainville 93230, France

Administration of a total dose of 2.0 µg of the new antiestrogen RU 16117 (ll-methoxy ethinyl estradiol) during the first two days of the cycle to rats showing a 4-day cycle delayed the time of ovulation and the appearance of vaginal cornification. A total dose of 5 µg of RU 16117 administered only at estrus led to a marked inhibition of the spontaneous peaks of LH, FSH and PRL measured on the afternoon of expected proestrus. Treatment with the antiestrogen led to a marked inhibition of the pituitary LH response to LH RH measured on the afternoon of expected proestrus, thus indicating that the steroid exerts an inhibitory action at the hypothalamo-pituitary level. The same treatment depressed the increase of uterine weight measured on the expected days of proestrus and estrus. A single dose of 5 µg of RU 16117 at different times of the estrous cycle showed that estrus is the period of maximal sensitivity to the inhibitory action of the steroid. The present data show that the antiestrogen RU 16117 can completely block ovulation and other parameters of the estrous cycle at low doses and that the inhibitory effect of the steroid is followed by a dose-dependent reappearance of normal estrous cycles after cessation of therapy.