Effects of an Estrogen Antagonist on Enzyme Activities and [³H]Estradiol Nuclear Binding in Uterus, Pituitary and Brain*

The estrogenic and anti-estrogenic properties of CI-628 in the uterus, pituitary and brain were assessed and compared with those of estradiol benzoate (EB) after in vivo administration to ovariectomized (OVX) rats by measuring changes in protein content, enzyme activities and [3H]- estradiol nuclear binding. 1) EB administration led to increased total protein and glucose-6-phosphate dehydrogenase (G6PDH) activity in the uterus and pituitary, increased choline acetylase (CAT) activity in the preoptic area and decreased monoamine oxidase (MAO) activity in the corticomedial amygdala (CMamygdala). 2) CI-628 mimicked all of the above changes except those in the pituitary. The CI-628 dependent changes in protein content and enzyme activities in the uterus were less than half of the EB changes. In the preoptic area and CM-amygdala, CI-628 resulted in approximately the same changes in CAT and MAO activity as EB. 3) In the pituitary and uterus, CI-628 antagonized the EB-dependent increase in G6PDH activity. In the CM-amygdala and preoptic area, CI-628 pretreatment did not antagonize the EB dependent changes in CAT and MAO. 4) CI-628 reduced nuclear binding of [3H]estradiol to approximately 5% of control in the uterus and pituitary and this effect lasted for at least 96 h. In contrast, CI-628 reduced nuclear binding in the preoptic area-hypothalamus-amygdala to 13% of control at 18 h after CI-628, but at 96 h nuclear binding of [3H]estradiol had recovered to 70% of control. Thus, the effect of CI-628 on these specific biochemical markers of estrogen action was not identical in the different target tissues. The possibility is discussed that the basis for the heterogeneity of responses may reside in the different time course of CI-628 interaction with cellular estrogen receptors in the target tissues.