Exploration of prostanoid receptor subtype regulating estradiol and prostaglandin E2 induction of spinophilin in developing preoptic area neurons
Exploration of prostanoid receptor subtype regulating estradiol and prostaglandin E2 induction of spinophilin in developing preoptic area neurons
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DOI：
10.1016/j.neuroscience.2007.02.006
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发表时间：
2007-05-25
期刊：
影响因子：
3.3
通讯作者：
McCarthy, M. M.
中科院分区：
文献类型：
--
作者：
Burks, S. R.;Wright, C. L.;McCarthy, M. M.
前列腺素E-2（PGE（2））介导雌二醇诱导的围产期敏感期大鼠性行为的雄性化。前列腺素E2诱导视前区（POA）神经元树突棘的形成，这种突触模式的变化与表达成年男性性行为的能力有关。PGE（2）是否从发育中的POA的星形胶质细胞或神经元释放尚不清楚。为了进一步了解PGE（2）如何在细胞水平诱导树突棘形成，我们探索了PGE（2）受体亚型介导的这种反应。PGE（2）有四种受体，即EP 1、EP 2、EP 3和EP 4，每种受体都具有独特但相互作用的信号转导谱。用EP受体激动剂伊洛前列素、布他前列素和硫前列酮治疗新生雌性大鼠表明，EP 2和EP 3受体的刺激显著增加了亲棘素，这种蛋白质的水平与树突棘的存在和POA的雄性化呈正相关。针对每种受体mRNA的反义寡核苷酸的使用揭示，在PGE（2）或雌二醇处理的雌性中，EP 2或EP 3受体敲低降低了亲棘素，而通过相同方法降低EP 1或EP 4受体水平具有较小但也显著的效果。EP受体表达的发育概况表明EP 1特别是在生命的最初几天升高，对应于雄性化的关键时期，而其他三种受体的mRNA水平保持相对恒定。(c)2007年IBRO。由爱思唯尔有限公司出版。保留所有权利。
The prostaglandin E-2 (PGE(2)) mediates estradiol-induced masculinization of sexual behavior in the rat during a perinatal sensitive period. PGE2 induces formation of dendritic spines on preoptic area (POA) neurons and this synaptic pattern change is associated with the ability to express male sexual behavior as an adult. Whether PGE(2) is released from astrocytes or neurons in the developing POA is unknown. To further understanding of how PGE(2) induces dendritic spine formation at the cellular level, we have explored the PGE(2) receptor subtype mediating this response. There are four receptors for PGE(2), EP1, EP2, EP3 and EP4, each having unique but interacting signal transduction profiles. Treatment of newborn female rats with the EP receptor agonists iloprost, butaprost and sulprostone indicated that stimulation of both the EP2 and EP3 receptors significantly increased spinophilin, a protein whose levels positively correlate to the presence of dendritic spines and masculinization of the POA. Use of antisense oligonucleotides against the mRNA for each receptor reveals that either EP2 or EP3 receptor knockdown reduces spinophilin in PGE(2)- or estradiol-treated females, whereas reducing EP1 or EP4 receptor levels by the same means has a smaller but also significant effect. A developmental profile of EP receptor expression indicates EP1 in particular is elevated for the first few days of life, corresponding to the critical period for masculinization, whereas mRNA levels for the other three receptors remain relatively constant. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.