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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.

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