Estrogen-induced signaling mechanisms involed in the establishment of the sexual dimorphysm of the rat brain

雌激素诱导的信号机制参与大鼠大脑性别二态性的建立

• 批准号: 22590214
• 负责人: KIYAMA Yuko
• 金额: $ 2.5万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010-10-20 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590214/
• 关键词: シグナル伝達; エストロゲン; マイクロアレイ; 脳の性分化; ラット; 能の性分化; エピジェネテック

In the rat brain, the sexually dimorphic nucleus (SDN) of the medial preoptic area (POA) is a major site for controlling sexual dimorphic behavior and physiological functions. The dimorphism is formed by the exposure to 17beta;-estradiol (E2) during the critical period, which begins around embryonic day 18. In order to explore key factors and mechanisms involved in the establishment of sex differences in response to E2, we prepared total RNA from brain slices containing SDN from female rats treated with E2 at birth, which was subjected to DNA microarray. The expression of the gene for protein kinase C-delta; (PKC-delta;) was significantly up-regulated by E2. We then examined the downstream effectors of PKC-delta; by Western blotting and immunohistochemistry, and found the involvement of the PKC-delta;/Rac1/LIMK1/cofilin pathway. This work demonstrated that cell migration enhanced by actin dynamics is a cue to create the sexual dimorphism in POA of the rat brain.

在大鼠脑内，视前内侧区（POA）的性二形核（SDN）是控制性二形行为和生理功能的主要部位。在胚胎第18天左右开始的关键期内，暴露于17 β-雌二醇（E2）可形成二态性。为了探讨E2诱导性别差异的关键因素和机制，我们从出生时接受E2处理的雌性大鼠脑片中提取了含有SDN的总RNA，并将其用于DNA微阵列。蛋白激酶C-δ（PKC-δ）基因的表达被E2显著上调。然后，我们通过Western印迹和免疫组织化学检查了PKC-δ的下游效应物，发现PKC-δ/Rac 1/LIMK 1/cofilin通路参与其中。这项工作表明，肌动蛋白动力学增强的细胞迁移是一个线索，创造性的二型性在POA的大鼠脑。

项目成果

Estrogen responsive genes in the preoptic area of the female rat during the critical period for sexual differentiation of the brain.

大脑性别分化关键期雌性大鼠视前区的雌激素反应基因。

• 发表时间: 2010
• 作者: Kiyama Y;他計5名中5位
• 通讯作者: 他計5名中5位

Estradiol-induced phosphorylation status of cofilin cascade and the establishment of the male-phenotype of the sexually dimorphic nucleus of the rat preoptic area

雌二醇诱导的丝切蛋白级联磷酸化状态及大鼠视前区性二形核雄性表型的建立

• 发表时间: 2011
• 作者: Wada-Kiyama Y.;他4名
• 通讯作者: 他4名

Estradiol-induced signaling involved in the sexual differentiation of the rat preoptic area.

雌二醇诱导的信号传导参与大鼠视前区的性别分化。

• 发表时间: 2010
• 作者: Suzuki C;他計5名中4位
• 通讯作者: 他計5名中4位

Actin dynamics in the sexually dimorphic nucleus of the rat preoptic area during the critical periods

关键期大鼠视前区性二形核肌动蛋白动态

• 发表时间: 2012
• 作者: Wada-Kiyama Y.;Suzuki C.;Hamada T.;Kiyama R.;Sakuma Y.
• 通讯作者: Sakuma Y.

雌ラット脳の性分化臨界期における視索前野のエストロゲン応答因子

雌性大鼠脑性别分化关键期视前区雌激素反应因素

• 发表时间: 2010
• 作者: 木山裕子;等5名
• 通讯作者: 等5名