近日,，日本的一個研究小組通過研究表示,，他們在動物實驗中發(fā)現(xiàn),，卵巢分泌的雌激素能激活腦神經(jīng)細胞中的一種蛋白質基因，從而促進排卵,。這一發(fā)現(xiàn)有望應用于不孕癥治療和促進家畜繁殖,。
名古屋大學副教授束村博子等人10日在美國《國家科學院學報》PNAS網(wǎng)絡版上報告說，她們給實驗鼠注入雌激素,，結果實驗鼠血中雌激素濃度上升導致大腦神經(jīng)細胞中的某基因大量編碼合成一種名為“kisspeptin”的蛋白質,，促進實驗鼠排卵。
研究小組還對比研究了即將排卵的20只實驗鼠和卵泡正在發(fā)育的20只實驗鼠的腦蛋白差異,。結果發(fā)現(xiàn),，與卵泡還在發(fā)育的實驗鼠相比，即將排卵的實驗鼠腦神經(jīng)細胞中的這種蛋白質水平是前者的數(shù)十倍,。
束村博子說,，充分了解雌激素和大腦神經(jīng)細胞在排卵中的具體作用，或許有助于將來“調動”某些腦神經(jīng)細胞,，以便調節(jié)雌激素水平,，為不孕癥治療和促進家畜繁殖開發(fā)新技術。（生物谷Bioon.com）
doi:10.1073/pnas.1114245109
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Epigenetic regulation of Kiss1 gene expression mediating estrogen-positive feedback action in the mouse brain
Junko Tomikawaa, Yoshihisa Uenoyamaa, Makiko Ozawaa, Tatsuya Fukanumaa, Kenji Takasea, Teppei Gotoa, Hitomi Abea, Nahoko Iedaa, Shiori Minabea, Chikaya Deuraa, Naoko Inouea, Makoto Sanbob, Koichi Tomitab, Masumi Hirabayashib, Satoshi Tanakac, Takuya Imamurad, Hiroaki Okamurae, Kei-ichiro Maedaf,1, and Hiroko Tsukamuraa,1,2
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.
