Honda S I, Matsumoto T, Harada N
Department of Biochemistry, School of Medicine, Fujita Health University, Kutsukake-cho, Toyoake, 470-1192, Aichi, Japan.
J Steroid Biochem Mol Biol. 2001 Dec;79(1-5):255-60. doi: 10.1016/s0960-0760(01)00142-x.
The functional differences between male and female brains commit to the existence of androgen that the testis secretes during the perinatal period. Androgen exerts its action on the brain after conversion to estrogen by brain aromatase. The aromatase appears in some neural nuclei such as in the hypothalamus and amygdala, and has been indicated to be involved in the expression of sexuality by the results of neurobehavioral analyses involving aromatase-knockout mice. We analyzed the brain-specific promoter in order to clarify the control mechanism for the expression of brain aromatase, which is deeply concerned in the sexual differentiation of the brain. The 202bp upstream region of brain-specific exon 1 contains at least three kinds of cis-acting elements, Arom-Aalpha, -Abeta and -B. In particular, the binding activities as to the Abeta sequence show a tissue-specific pattern. Gel shift analysis revealed that the Abeta binding factor recognizes the TTGGCCCCT sequence. Abeta binding activity is detectable at the perinatal stage, but is undetectable at the adult stage in the brain. Furthermore, a protein which binds to the Abeta sequence was purified from the fetal mouse brain. The molecular mass of the Abeta binding protein was estimated to be 49kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
雄性和雌性大脑之间的功能差异归因于围产期睾丸分泌的雄激素的存在。雄激素在被脑芳香化酶转化为雌激素后对大脑发挥作用。芳香化酶出现在一些神经核团中，如下丘脑和杏仁核，并且涉及芳香化酶基因敲除小鼠的神经行为分析结果表明其参与了性行为的表达。我们分析了大脑特异性启动子，以阐明大脑芳香化酶表达的调控机制，该酶与大脑的性别分化密切相关。大脑特异性外显子1上游202bp区域至少包含三种顺式作用元件，即芳香化酶Aα、Aβ和B。特别是，与Aβ序列的结合活性呈现出组织特异性模式。凝胶迁移分析表明，Aβ结合因子识别TTGGCCCCT序列。Aβ结合活性在围产期阶段可检测到，但在成年大脑中无法检测到。此外，从胎鼠大脑中纯化出了一种与Aβ序列结合的蛋白质。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳估计，Aβ结合蛋白的分子量为49kDa。
