LONG-TERM EFFECTS OF ESTROGEN ACTION ARE CRUCIAL FOR THE DISPLAY OF LORDOSIS IN FEMALE GUINEA-PIGS - ANTAGONISM BY ANTI-ESTROGENS AND CORRELATIONS WITH INVITRO CYTOPLASMIC BINDING ACTIVITY

The administration of 1.6 μg 17β-estradiol benzoate (EB) 60 h before an injection of 0.5 mg progesterone induced optimal lordosis responses in ovariectomized guinea pigs. To determine whether the presence of estrogen in neural tissue throughout the 60-h period was necessary for the display of lordosis, various antiestrogens (i.e. MER-25, CI-628, enclomiphene, or zuclomiphene) were administered during the late portion of the 60-h period. Dose-dependent inhibition of lordosis resulted when these antiestrogens were injected at 40 and 47 h after EB injection. On the other hand, injection of supplemental EB late in the priming period enhanced the display of lordosis. A correlation between behavioral antiestrogenicity and in vitro competition for cytoplasmic hypothalamic-preoptic area (H-POA) estrogen receptors was observed for all of the antiestrogens tested except MER-25. The rank order of behavioral antiestrogenic activity was: CI-628 > MER-25 = enclomiphene > zuclomiphene. The relative binding affinities of each compound compared to E2 were: CI-628, 2.80; enclomiphene, 1.94; zuclomiphene, 0.05; and MER-25, 0.00089. These results suggest that the uninterrupted action of estrogen in hypothalamicpreoptic area neurons during the period just before and/or during the time of progesterone action is necessary for optimal display of lordosis in guinea pigs. © 1979 by The Endocrine Society.