A series of experiments assessed whether the ability of the
antiestrogen CI-628 to inhibit
estrogen-stimulated
lordosis in adult ovariectomized rats depends upon its interference with the synergistic effects of
estrogen with
progesterone. In Experiment 1, the effect of
CI-628 was contrasted in rats brought into estrus by a single
subcutaneous injection of
estradiol benzoate (EB) combined with an injection of
progesterone (P) 42 hr later versus four daily
injections of EB (without any P).
CI-628 was given at the time of EB injection(s).
CI-628 substantially and equally effectively antagonized lordotic responding in both conditions. In the absence of
CI-628, rats receiving
progesterone had significantly higher
lordosis scores than the 4-day EB control animals. In Experiment 2, rats receiving
CI-628 on only the first 2 of 4 days of EB
injections had significantly decreased
lordosis scores unless P was also given on the day of testing. This suggested that the EB from the latter
injections was not acting as a
progestin "mimic." In Experiment 3, lordotic responding stimulated by EB (without P) was inhibited by
CI-628 in rats that were both ovariectomized and adrenalectomized. This suggested that adrenal
progestins were not involved in the ability of
CI-628 to inhibit
lordosis. Taken together, the results suggest that the mechanism of action of
CI-628 for the inhibition of
lordosis does not depend upon its ability to antagonize an
estrogen-induced increase in neural
progestin receptors. Implications of this for
estrogen-mediated behaviors, for which
CI-628 has little or no antagonistic effects, are discussed.