Estrogen-induced cell signaling in the sexually dimorphic nucleus of the rat preoptic area: potential involvement of cofilin in actin dynamics for cell migration
Estrogen-induced cell signaling in the sexually dimorphic nucleus of the rat preoptic area: potential involvement of cofilin in actin dynamics for cell migration
复制标题
雌激素诱导的大鼠视前区性二形核中的细胞信号传导：肌动蛋白丝切蛋白可能参与细胞迁移的肌动蛋白动力学
DOI：
10.1016/j.bbrc.2013.02.117
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发表时间：
2013
影响因子：
3.1
通讯作者：
Sakuma Y
中科院分区：
文献类型：
--
作者：
Wada-Kiyama Y;Suzuki C;Hamada T;Rai D;Kiyama R;Kaneda M;Sakuma Y
雌激素是诱导大鼠脑视前区（POA）性二形核（SDN）形成的关键因素。在POA的关键期，在SDN的雌激素依赖性信号通路的识别是阐明机制的先决条件。在本研究中，我们在出生时（指定为出生后第1天（P1））用/不用17β-雌二醇（E2）处理雌性大鼠，并从含有SDN的脑切片中制备总RNA用于DNA微阵列分析。在所鉴定的雌激素应答基因中，蛋白激酶C-δ（PKC-δ）在P5被E2显著上调。通过Western blotting检测PKC-δ蛋白的下游效应子，发现E2诱导的PKC-δ/Rac 1/PAK 1/LIMK 1/cofilin通路。在该通路中，E2抑制cofilin的磷酸化（非活性形式）。这一结果得到了免疫组织化学的支持，其中cofilin的磷酸化/去磷酸化发生在SDN，这表明细胞迁移是POA中产生性二型性的线索。
Estrogen is a key factor to induce the sexually dimorphic nucleus (SDN) in the preoptic area (POA) of the rat brain. Identification of estrogen-dependent signaling pathways at SDN in POA during the critical period is a prerequisite for elucidating the mechanism. In the present study, we treated female rats with/without 17β-estradiol (E2) at birth, designated as postnatal day 1 (P1), and prepared total RNA from brain slices containing SDN for DNA microarray analysis. Among the estrogen-responsive genes identified, protein kinase C-delta (PKC-δ) was significantly up-regulated by E2at P5. We examined the downstream effectors of PKC-δ protein by Western blotting and found an E2-induced PKC-δ/Rac1/PAK1/LIMK1/cofilin pathway. In the pathway, E2suppressed the phosphorylation (inactive form) of cofilin. This result was supported by immunohistochemistry, where the phosphorylation/dephosphorylation of cofilin occurred at SDN, which suggests that cell migration is a cue to create sexual dimorphism in POA.