Michael R P, Bonsall R W, Rees H D
Endocrinology. 1986 May;118(5):1935-44. doi: 10.1210/endo-118-5-1935.
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 less than 0.01) in nuclei from preoptic area and amygdala compared with control values and by 78% (P less than 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.
为了鉴定从雌性灵长类动物大脑中获取的细胞核内雌二醇（E2）和睾酮（T）的代谢产物，进而研究它们对行为的作用机制，我们对9只成年去卵巢恒河猴进行了研究。其中两只雌性猴子注射了5.5毫居里的[3H]T，30分钟后，取出14个脑区、垂体和外周组织的样本并进行匀浆。制备纯化的细胞核和粗制的胞质溶胶部分，用乙醚提取，然后通过高效液相色谱法进行分离，以鉴定类固醇代谢产物。在下丘脑、视前区和杏仁核的细胞核中，局部形成的[3H]E2是放射性的主要形式。在阴蒂的细胞核中，[3H]二氢睾酮是放射性的主要形式，而在所有其他脑样本以及垂体和子宫的细胞核中，[3H]T占主导地位。两只雌性猴子（对照组）皮下注射油剂预处理5天，注射1毫居里的[3H]E2，60分钟后处死。在这些雌性猴子中，下丘脑、视前区、杏仁核、垂体和子宫的细胞核中[3H]E2的核浓度升高。在用2毫克/天丙酸二氢睾酮皮下预处理5天，然后注射1毫居里[3H]E2的另外两只雌性猴子中也得到了类似的结果。在用2毫克/天丙酸睾酮皮下预处理5天，然后注射1毫居里[3H]E2的三只雌性猴子中，与对照值相比，视前区和杏仁核细胞核中[3H]E2的水平降低了100%（P<0.01），下丘脑细胞核中降低了78%（P<0.05）。大脑皮层、垂体或子宫中的类固醇水平没有类似的降低。这是雌性灵长类动物大脑中首次直接证明T和E2的作用涉及相同的受体系统。
