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首页> 外文期刊>Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism >Androgenic/estrogenic balance in the male rat cerebral circulation: metabolic enzymes and sex steroid receptors.
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Androgenic/estrogenic balance in the male rat cerebral circulation: metabolic enzymes and sex steroid receptors.

机译:雄性大鼠脑循环中的雄激素/雌激素平衡:代谢酶和性类固醇受体。

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摘要

Tissues from males can be regulated by a balance of androgenic and estrogenic effects because of local metabolism of testosterone and expression of relevant steroid hormone receptors. As a critical first step to understanding sex hormone influences in the cerebral circulation of males, we investigated the presence of enzymes that metabolize testosterone to active products and their respective receptors. We found that cerebral blood vessels from male rats express 5alpha-reductase type 2 and aromatase, enzymes responsible for conversion of testosterone into dihydrotestosterone (DHT) and 17beta-estradiol, respectively. Protein levels of these enzymes, however, were not modulated by long-term in vivo hormone treatment. We also showed the presence of receptors for both androgens (AR) and estrogens (ER) from male cerebral vessels. Western blot analysis showed bands corresponding to the full-length AR (110 kDa) and ERalpha (66 kDa). Long-term in vivo treatment of orchiectomized rats with testosterone or DHT, but not estrogen, increased AR levels in cerebral vessels. In contrast, ERalpha protein levels were increased after in vivo treatment with estrogen but not testosterone. Fluorescent immunostaining revealed ERalpha, AR, and 5alpha-reductase type 2 in both the endothelial and smooth muscle layers of cerebral arteries, whereas aromatase staining was solely localized to the endothelium. Thus, cerebral vessels from males are target tissues for both androgens and estrogen. Furthermore, local metabolism of testosterone might balance opposing androgenic and estrogenic influences on cerebrovascular as well as brain function in males.
机译:由于睾丸激素的局部代谢和相关类固醇激素受体的表达,雄性组织可以通过雄激素和雌激素作用的平衡来调节。作为了解性激素对男性大脑循环的影响的关键的第一步,我们研究了将睾丸酮代谢成活性产物及其各自受体的酶的存在。我们发现,雄性大鼠的脑血管表达5α-还原酶2型和芳香酶,这些酶分别负责将睾丸激素转化为二氢睾丸激素(DHT)和17β-雌二醇。但是,这些酶的蛋白质水平并未受到体内长期激素治疗的调节。我们还显示了雄性脑血管中雄激素(AR)和雌激素(ER)受体的存在。蛋白质印迹分析显示对应于全长AR(110 kDa)和ERalpha(66 kDa)的条带。用睾丸激素或DHT(但不是雌激素)对睾丸切除的大鼠进行长期体内治疗会增加脑血管的AR水平。相反,在体内用雌激素而不是睾丸激素治疗后,ERalpha蛋白水平升高。荧光免疫染色显示在脑动脉的内皮层和平滑肌层均存在ERalpha,AR和5alpha还原酶2型,而芳香化酶染色仅定位于内皮。因此,雄性的脑血管是雄激素和雌激素的靶组织。此外,睾丸激素的局部代谢可能平衡雄性对脑血管和脑功能的相反的雄激素和雌激素影响。

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