导读：日本的一个研究小组日前说，他们在动物实验中发现，卵巢分泌的雌激素能激活脑神经细胞中的一种蛋白质基因，从而促进排卵。这一发现有望应用于不孕症治疗和促进家畜繁殖。
日本的一个研究小组日前说，他们在动物实验中发现，卵巢分泌的雌激素能激活脑神经细胞中的一种蛋白质基因，从而促进排卵。这一发现有望应用于不孕症治疗和促进家畜繁殖。
名古屋大学副教授束村博子等人4月10日在美国《国家科学院院刊》网络版上报告说，她们给实验鼠注入雌激素，结果实验鼠血中雌激素浓度上升导致大脑神经细胞中的某基因大量编码合成一种名为“kisspeptin”的蛋白质，促进实验鼠排卵。
研究小组还对比研究了即将排卵的20只实验鼠和卵泡正在发育的20只实验鼠的脑蛋白差异。结果发现，与卵泡还在发育的实验鼠相比，即将排卵的实验鼠脑神经细胞中的这种蛋白质水平是前者的数十倍。
束村博子说，充分了解雌激素和大脑神经细胞在排卵中的具体作用，或许有助于将来“调动”某些脑神经细胞，以便调节雌激素水平，为不孕症治疗和促进家畜繁殖开发新技术。
Epigenetic regulation of Kiss1 gene expression mediating estrogen-positive feedback action in the mouse brain
Junko Tomikawa, Yoshihisa Uenoyama, Makiko Ozawa, Tatsuya Fukanuma, Kenji Takase, Teppei Goto, Hitomi Abe, Nahoko Ieda, Shiori Minabe, Chikaya Deura, Naoko Inoue, Makoto Sanbo, Koichi Tomita, Masumi Hirabayashi, Satoshi Tanaka, Takuya Imamura, Hiroaki Okamura, Kei-ichiro Maeda, and Hiroko Tsukamura
This study aims to determine the epigenetic mechanism regulating Kiss1 gene expression in the anteroventral periventricular nucleus (AVPV) to understand the mechanism underlying estrogen-positive feedback action on gonadotropin-releasing hormone/gonadotropin surge. We investigated estrogen regulation of the epigenetic status of the mouse AVPV Kiss1 gene locus in comparison with the arcuate nucleus (ARC), in which Kiss1 expression is down-regulated by estrogen. Histone of AVPV Kiss1 promoter region was highly acetylated, and estrogen receptor α was highly recruited at the region by estrogen. In contrast, the histone of ARC Kiss1 promoter region was deacetylated by estrogen. Inhibition of histone deacetylation up-regulated in vitro Kiss1 expression in a hypothalamic non–Kiss1-expressing cell line. Gene conformation analysis indicated that estrogen induced formation of a chromatin loop between Kiss1 promoter and the 3′ intergenic region, suggesting that the intergenic region serves to enhance estrogen-dependent Kiss1 expression in the AVPV. This notion was proved, because transgenic reporter mice with a complete Kiss1 locus sequence showed kisspeptin neuron-specific GFP expression in both the AVPV and ARC, but the deletion of the 3′ region resulted in greatly reduced GFP expression only in the AVPV. Taken together, these results demonstrate that estrogen induces recruitment of estrogen receptor α and histone acetylation in the Kiss1 promoter region of the AVPV and consequently enhances chromatin loop formation of Kiss1 promoter and Kiss1 gene enhancer, resulting in an increase in AVPV-specific Kiss1 gene expression. These results indicate that epigenetic regulation of the Kiss1 gene is involved in estrogen-positive feedback to generate the gonadotropin-releasing hormone/gonadotropin surge.
文献链接：https://www.pnas.org/content/early/2012/04/05/1114245109
