Abstract
Groups of ovariectomized mice were pretreated for 30 min with either vehicle, unlabeled estradiol benzoate or one of the following anti-hormones: cyproterone acetate, CI-628 or CN-69, 725-27. One hour after an I.V. injection of [3H]estradiol the levels of toluence extractable radioactivity retained in the crude nuclear and cytosol fractions of selected brain regions, pituitary and plasma were determined by liquid scintillation spectrometry. The major findings were: (1) In vehicle treated animals [3H]estradiol uptake in the pituitary greatly exceeded that in all brain regions. Within the brain uptake was greatest in the preoptic anterior hypothalamus (POA-AH) and medial basal hypothalamus (MBH) samples. Nuclear uptake exceeded cytosol uptake only in the pituitary and POA-AH and MBH samples. (2) Estradiol benzoate pretreatment greatly reduced nuclear, and to a lesser extent cytosol [3H]estradiol uptake in pituitary, POA-AH and MBH samples. Estradiol benzoate pretreatment also reduced nuclear uptake in the dorsal middle hypothalamus (DMH). (3) The anti-androgen cyproterone acetate, previously shown to have anti-estrogenic effects in female sexual behavior tests, was found to have no effect on nuclear or cytosol [3H]estradiol uptake in brain and pituitary. (4) The anti-estrogen CI-628 was found to reduce nuclear [3H]estradiol uptake in the POA-AH and pituitary samples. It also reduced cytosol [3H]estradiol uptake in the pituitary sample. The anti-estrogen CN-69, 725-27 produced a much greater inhibition of nuclear [3H]estradiol uptake than CI-628 in the POA-AH, MBH, DMH, dorsal posterior hypothalamus and pituitary samples. This anti-estrogen also reduced cytosol [3H]estradiol uptake in the POA-AH, MBH and pituitary samples. (5) A preliminary chromatographic analysis of vehicle control samples indicated that 70-98% of the nuclear radioactivity in target regions such as POA-AH, MBH and pituitary was iso-polar with authentic estradiol, while less than 50% of the radioactivity in plasma and cortex behaved as estradiol.
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