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The Nuclear Accumulation of [³H]Testosterone and [³H] Estradiol in the Brain of the Female Primate: Evidence for the Aromatization Hypothesis^*

Department of Psychiatry, Emory University School of Medicine Atlanta, Georgia 30322
Georgia Mental Health Institute Atlanta, Georgia 30306

Address requests for reprints to: Richard P. Michael, M.D., Department of Psychiatry, Emory University School of Medicine, Atlanta, Georgia 30322.

Abstract

To identify the metabolites of estradiol (E₂) and testosterone (T) in nuclei obtained from the female primate brain and, hence, to investigate the mechanism of their actions on behavior, 9 ovariectomized adult rhesus monkeys were studied. Two of these females were injected with 5.5 mCi [³H]T, and 30 min later, samples of 14 brain areas, pituitary gland, and peripheral tissues were removed and homogenized. Purified cell nuclei and a crude cytosol fraction were prepared, extracted with ether, and fractionated by HPLC to identify steroid metabolites. In nuclei from the hypothalamus, preoptic area, and amygdala, [³H]E₂ formed locally was the major form of radioactivity. In nuclei from the clitoris, [³H]dihydrotestosterone was the major form of radioactivity, and in nuclei in all other brain samples and in the pituitary gland and uterus, [³H]T predominated. Two females (controls) were pretreated for 5 days with oil sc, injected with 1 mCi [³H]E₂, and killed 60 min later. In these females, elevated nuclear concentrations of [³H]E₂ were found in the hypothalamus, preoptic area, amygdala, pituitary gland, and uterus. Similar results were obtained in 2 females that were pretreated for 5 days with 2 mg/day dihydrotestosterone propionate, sc, and then injected with 1 mCi [³H]E₂. In 3 females that were pretreated for 5 days with 2 mg/day T propionate, sc, and then injected with 1 mCi [³H]E₂, levels of [³H]E₂ were reduced by 100% (P < 0.01) in nuclei from preoptic area and amygdala compared with control values and by 78% (P < 0.05) in nuclei from the hypothalamus. There were no comparable reductions in steroid levels in cerebral cortex, pituitary gland, or uterus. This is the first direct evidence in the brain of a female primate that the actions of T and E₂ involve the same receptor systems. (Endocrinology 118: 1935–1944, 1986)

Footnotes

^* This work was supported by USPHS Grant MH-19506 and general research support was provided by the Georgia Department of Human Resources.

Received June 25, 1985.

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