Binding of [3-H]estradiol by brain cell nuclei and female rat sexual behavior: inhibition by antiestrogens
Roy, E.J.; Wade, G.N.
Brain Research 126(1): 73-87
1977
ISSN/ISBN: 0006-8993 PMID: 856418 DOI: 10.1016/0006-8993(77)90216-5Document Number: 435253
In order to clarify the relationship between estradiol binding in the brain and its behavior actions, the effects of 3 antiestrogens (MER-25, CI-628, and nafoxidine) on in vivo tritiated estradiol uptake and retention in cell nuclear fractions or regions of the brain and pituitary were investigated. The ability of antiestrogens to block estradiol-induced female sexual behavior was also studied. Antiestroge were injected 2 hours prior to injection of tritiated estradiol and animals killed 2 hours later. Radioactivity in whole homogenates and isolated cell nuclei of cerebral cortex, hypothalamus, preoptic area-suptum, and pituitary was reduced by CI-628. Nafoxidine reduced uptake in cell nuclei of the hypothalamus, preoptic area-septum, and pituitary. MER-25 only inhibited uptake in the pituitary. CI-628 and nafoxidine totally inhibited lordosis while MER-25 was ineffective when injected 2 hours prior to testing. However, when MER-25 was injected 12 hours prior to testing it inhibited retention of tritiated estradiol in brain and pituitary cell nuclei and lordosis response. When antiestrogens were injected prior to estradiol injection all had greater inhibition of nuclear estradiol retention at 12 hours after the estradiol injection than at 2 hours. When CI-628 was injected 2 hours following injection of tritiated estradiol, most of the radioactivity present in the hypothalamic preoptic area nuclei at 12 hours after the estradiol injection was displaced. Thus antiestrogens can prevent or reverse the nuclear concentration of estradiol in the brain. Female sexual behavior seems to be induced by the presence of estradiol in the cell nucleus.