Effect of subcutaneous vs intraperitoneal administration of an anti-estrogen, CI-628, on estradiol- and estradiol benzoate-stimulated lordosis in the ovariectomized rat

Abstract

The anti-estrogen CI-628 (3 mg) inhibited estradiol (E, 150 μg, SC in oil)-stimulated lordosis in ovariectomized rats, when the anti-estrogen was given intraperitoneally (IP) at the time of E injection (Hr 0). No lordosis inhibition occurred after similar treatment, if the CI-628 was given subcutaneously. For estradiol benzoate (EB, 2 μg, SC in oil)-stimulated lordosis, CI-628 (Hr 0) had a substantial inhibitory effect whether it was given IP or SC, the greater percentage inhibition occurring after SC CI-628 (Experiment 1). All animals received sequential injections of estrogen and progesterone (500=s,g, SC in oil) and were then tested to 10 mounts by an intact male. These results suggested that, after E injection, neural tissues mediating lordosis have a shorter period of sensitivity to the behavioral effects of CI-628 than after EB injection. Thus, inhibition of E-stimulated lordosis apparently required the more rapid onset of intracellular estrogen retention inhibition resulting from CI-628 given IP rather than SC. This was not the case for EB-stimulated lordosis, where a longer period of sensitivity to CI-628 seemed likely. This hypothesis was supported by the data of Experiment 2, in which CI-628 (3 mg, IP) was first given 3 hr after E or EB treatment. In this paradigm, CI-628 no longer inhibited E-stimulated lordosis. In contrast, the anti-estrogen's effect on EB-stimulated lordosis was at least equal to the inhibition occurring after CI-628 (IP) given at Hr 0.