Anti-estrogen effects on estrogen accumulation in brain cell nuclei: Neurochemical correlates of estrogen action on female sexual behavior in guinea pigs

The presence of estrogen in brain and peripheral target tissues was monitored with respect to the display of sexual behavior in female guinea pigs. Temporal and quantitative aspects of estrogen accumulation in cell nuclei of cerebral cortex, hypothalamic-preoptic areas ( H-POA), and pituitary of ovariectomized guinea pigs were determined after s.c. administration of [ 3Hestradiol benzoate ([ 3HEB) (100 μCi [ 3HEB plus 0.8 μg unlabeled EB). Nuclear accumulation of estrogen followed the pattern:pituitary>H-POA>cortex. Peak nuclear accumulation of estrogen in the pituitary occurred at 20 h after [ 3HEB and then levels declined. In the nuclear fraction of H-POA, estrogen accumulation reached a peak by 11 h after [ 3HEB injection and remained at peak values 43 h after [ 3HEB. Nuclear accumulation of estrogen in the cortex was minimal. The accumulation of estrogen in whole homogenates and cell nuclei of brain and peripheral target tissues was assessed during the display of sexual behavior in EB-progesterone (P)-treated animals. [ 3HEB was injected s.c. at 0 h and P (0.5 mg) was administered at 39 h. At the first display of lordosis the animals were killed and estrogen accumulation determined. No effect of P on estrogen retention in cell nuclei or whole homogenates could be detected. Additionally, the effects of the anti-estrogens, enclomiphene (ENC) and CI-628, on estrogen uptake and retention in brain and peripheral target tissues were determined. Using a treatment schedule of ENC known to inhibit EB-induced sexual behavior (4 serial injections of ENC 48 h prior to EB), estrogen accumulation was significantly reduced in whole homogenates of H-POA, pituitary, and uterus both at 2 h and 39 h after [ 3HEB injextion. Nuclear accumulation was also suppressed in the pituitary and uterus at both time points while nuclear inhibition of H-POA was apparent only at 39 h. Similar treatment with CI-628, which does not inhibit EB-induced sexual behavior in guinea pigs, also did not inhibit uptake in the H-POA. CI-628 suppressed estrogen accumulation in the pituitary and uterus by 39 h after [ 3HEB. Using a treatment schedule of ENC known to facilitate the priming action of EB for the display of lordosis (2 serial injections of ENC 28 h prior to EB), estrogen accumulation in the H-POA was not affected at either 2 h or 11 h after [ 3HEB injection. However, this treatment reduced whole homogenate uptake in the pituitary and uterus (at 11 h) and nuclear accumulation in the pitui