Brain estradiol content in newborn rats:: Sex differences, regional heterogeneity, and possible de novo synthesis by the female telencephalon
Brain estradiol content in newborn rats:: Sex differences, regional heterogeneity, and possible de novo synthesis by the female telencephalon
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DOI：
10.1210/en.2003-1363
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发表时间：
2004-06-01
期刊：
影响因子：
4.8
通讯作者：
McCarthy, MM
中科院分区：
文献类型：
--
作者：
Amateau, SK;Alt, JJ;McCarthy, MM
在发育中的大脑性腺类固醇水平的准确评估是至关重要的理解自然发生的类固醇介导的性分化，以及确定在这种现象的研究中常用的外源性类固醇治疗的生理相关性。使用RIA，我们测量了雌二醇（E-2）含量的6个区域的发育中的大脑产后立即，产后1天，注射外源性苯甲酸雌二醇，丙酸睾酮，或芳香酶抑制剂福美司坦后。我们在新生儿大脑的几个区域发现了性二态的E-2含量。在2小时的生活，有显着较高的E-2含量在男性比女性在额叶皮层，下丘脑和视前区，但不是在海马，脑干，或小脑。令人惊讶的是，女性海马体的E-2含量明显高于所有其他女性区域。到产后第1天，大多数脑区的E-2水平急剧下降，只有下丘脑保持了性别差异。注射雌性幼鼠的苯甲酸雌二醇使下丘脑的组织水平升高到雄性幼鼠的水平，但在其他五个区域中升高了2至3倍。替吉奥管理增加E-2含量只在视前区，这表明芳香酶活性和/或底物的可用性的局部变化。福美坦的中枢给药降低了雄性皮质、下丘脑和视前区的雌激素含量。福美坦给药还降低了雌性皮质和海马中的内源性E-2，表明这些脑区选择性从头合成。这些数据证实并扩展了以前的研究结果，性别差异的大脑E-2水平围产期，并揭示了意外的区域异质性E-2合成和/或代谢。
Accurate assessment of gonadal steroid levels in the developing brain is critical for understanding naturally occurring steroid-mediated sexual differentiation as well as determining the physiological relevance of exogenous steroid treatments commonly used in the study of this phenomenon. Using RIA, we measured the estradiol (E-2) content of six regions of the developing brain immediately post partum, 1 d post partum, and after injection of exogenous estradiol benzoate, testosterone propionate, or the aromatase inhibitor formestane. We found sexually dimorphic E-2 content in several regions of the newborn brain. At 2 h of life, there was significantly higher E-2 content in males vs. females in the frontal cortex, hypothalamus and preoptic area but not in the hippocampus, brainstem, or cerebellum. Surprisingly, the female hippocampus had significantly higher E-2 content than all other female regions examined. By d 1 postpartum, E-2 levels had decreased precipitously in most brain regions, and only the hypothalamus maintained a sex difference. Injection of female pups with estradiol benzoate raised tissue levels to that of the male in the hypothalamus but 2- to 3-fold higher in the other five regions. Testosterone administration increased E-2 content exclusively in the preoptic area, suggesting local variation in aromatase activity and/or substrate availability. Central administration of formestane decreased estrogen content in the male cortex, hypothalamus, and preoptic area. Formestane treatment also decreased endogenous E-2 in female cortex and hippocampus, suggesting de novo synthesis selectively in these brain regions. These data corroborate and extend previous findings of sex differences in brain E-2 levels perinatally and reveal tin unexpected regional heterogeneity in E-2 synthesis and/or metabolism.