Expression of EAP1 and CUX1 in the hypothalamus of female rats and relationship with KISS1 and GnRH

Expression of EAP1 and CUX1 in the hypothalamus of female rats and relationship with KISS1 and GnRH
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雌性大鼠下丘脑EAP1、CUX1的表达及其与KISS1、GnRH的关系

DOI:
10.1507/endocrj.ej16-0123
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发表时间:
2016-08-20
期刊:
影响因子:
2
通讯作者:
Li, Pin
Li, Pin
中科院分区:
医学4区
文献类型:
--
作者:
Xu, Jing;Li, Pin

文献摘要

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使用高通量和生物信息学策略的组合,结合系统生物学方法,从非人灵长类动物和大鼠的下丘脑中挑选出一组相关基因,包括EAP 1和CUX 1,其表达在雌性青春期时增加。推测EAP 1和CUX 1基因可能通过调控KISS 1基因的表达而参与女性青春期的适时启动。因此,我们测量了下丘脑的EAP1和CUX1基因的表达在mRNA和蛋白质水平沿着各自的免疫反应细胞的数量在三个不同的发展阶段(青少年,青春期早期和成年)的雌性SD大鼠。此外,我们还观察了它们的免疫反应细胞的分布。下丘脑中EAP1和CUX1的mRNA水平在不同性发育阶段无明显变化,但EAP1的蛋白表达在青春早期组显著高于青春期组。此外,我们发现EAP 1和CUX 1基因定位于神经元细胞核。两者均在大鼠下丘脑弓状核(ARC)细胞中显著表达,这也是KISS 1基因的主要定位。CUX1基因在kisspeptin神经元中共表达。此外,EAP 1免疫反应阳性细胞的数量和百分比在青春早期组均显著高于青少年组。以上结果提示EAP1基因可能参与了女性青春期的神经内分泌调控,并与kisspeptin信号通路相关。
Using a combination of high throughput and bioinformatics strategies, in combination with a system biology approach, a group of related genes including EAP1 and CUX1 whose expression increased at the time of female puberty were singled out from the hypothalamus of nonhuman primates and rats. It was hypothesized that EAP1 and CUX1 genes may be required for the timely initiation of female puberty by regulating the expression of KISS1 gene. Therefore, we measured the hypothalamic expression of EAP1 and CUX1 genes of female SD rats in mRNA and protein levels along with the numbers of respective immunoreactive cells at three different development stages (juvenile, early puberty and adult). Besides, we investigated the distribution of their immunoreactive cells. Although there was no changes in the mRNA levels of EAP1 and CUX1 in the hypothalamus during the different sexual development stages, the protein expression of EAP1 in the early-puberty group was significantly higher than that in the juvenile group. Moreover, we found that EAP1 and CUX1 genes were localized in neuronal nuclei. Both were prominent in cells of the the arcuate nucleus (ARC) of the rat hypothalamus which was also the main localization of KISS1 gene. Especially, CUX1 gene was co-expressed in the kisspeptin neurons. Furthermore, the number and percentage of EAP1 immunoreactive cells in the early-puberty group were both significantly more than the juvenile group. Above results indicate that EAP1 gene may be involved in the neuroendocrine control of female puberty in correlation with the kisspeptin signaling.