Microarray analysis of neonatal rat anteroventral periventricular transcriptomes identifies the proapoptotic Cugbp2 gene as sex-specific and regulated by estradiol.
Microarray analysis of neonatal rat anteroventral periventricular transcriptomes identifies the proapoptotic Cugbp2 gene as sex-specific and regulated by estradiol.
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对新生大鼠前腹侧脑室周围转录组的微阵列分析确定促凋亡 Cugbp2 基因具有性别特异性并受雌二醇调节。
DOI：
10.1016/j.neuroscience.2015.07.008
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发表时间：
2015
期刊：
影响因子：
3.3
通讯作者：
Petersen,SL
中科院分区：
文献类型：
--
作者：
DelPinoSans,J;Krishnan,S;Aggison,LK;Adams,HL;Shrikant,MM;López-Giráldez,F;Petersen,SL
两性二态神经结构调节许多性别特异性功能，包括黄体生成素（LH）释放模式。女性的循环释放模式是由腹侧脑室周围核（AVPV）控制的，这是一个视前区（POA）区域，在男性中明显更小。用于解释这些结构和功能差异的主流假设是，“默认的”女性化AVPV通过暴露于雌二醇（E2）而去女性化，雌二醇是围产期睾丸产生的睾酮(T)的代谢物。e2暴露最终导致雄性AVPV细胞凋亡，但上游途径尚不清楚。为了解决这个问题，我们比较了出生后第2天（PND2）雄性和雌性与e2或载体处理的雌性的AVPV转录组。在PND2 AVPV中，89个性别特异性基因中只有6个也被e2调控，而e2调控的280多个基因未被发现是性别特异性的。在雄性和e2处理的雌性中发生相似变化的靶标中，编码CUG三重重复rna结合蛋白2 （Cugbp2）的基因表现出最高的折叠变化。定量聚合酶链反应（QPCR）研究证实PND2雄性和e2处理的雌性avpv中mRNA水平较高，e2诱导细胞凋亡。POA定位研究在AVPV和POA性别二态核（SDN-POA）中检测到Cugbp2 mRNA；然而，性别差异和e2效应仅发生在AVPV中。结合Cugbp2调节与性别分化相关的mrna的剪接和翻译的证据，我们提出该基因介导e2依赖性的AVPV去雌性化作用。
Sexually dimorphic neural structures regulate numerous gender-specific functions including luteinizing hormone (LH) release patterns. The female cyclic surge pattern of release is controlled by the anteroventral periventricular nucleus (AVPV), a preoptic area (POA) region that is significantly smaller in males. The prevailing hypothesis used to explain these differences in structure and function is that a “default” feminine AVPV is defeminized by exposure to estradiol (E2), a metabolite of testosterone (T) produced by the perinatal testes. E2exposure then culminates in apoptosis in the male AVPV, but the upstream pathways are poorly understood. To address this issue, we compared AVPV transcriptomes of postnatal day 2 (PND2) males and females with those of females treated with E2or vehicle. Only six of 89 sex-specific genes were also regulated by E2in the PND2 AVPV and E2regulated over 280 genes not found to be sex-specific. Of targets that changed similarly in males and E2-treated females, the gene encoding CUG triplet repeat, RNA-binding protein 2 (Cugbp2), a proapoptotic protein, showed the highest fold-changes. Quantitative polymerase chain reaction (QPCR) studies confirmed higher mRNA levels in PND2 male and E2-treated female AVPVs wherein E2induces apoptosis. POA mapping studies detected Cugbp2 mRNA in the AVPV and in the sexually dimorphic nucleus of the POA (SDN–POA); however, sex differences and E2effects occurred only in the AVPV. Combined with evidence that Cugbp2 regulates splicing and translation of mRNAs linked to sexual differentiation, we propose that this gene mediates E2-dependent effects on AVPV defeminization.