吻素
弓状核
核心
雌激素受体α
神经元
雌激素受体
生物
内科学
内分泌学
下丘脑
雌激素
促性腺激素释放激素
抑制因子
转录因子
细胞生物学
激素
神经科学
促黄体激素
基因
遗传学
医学
乳腺癌
癌症
作者
José M. Ramos Pittol,Isabel Fernandes-Freitas,Alexandra Milona,Stephen Manchishi,Kara Rainbow,Brian Y.H. Lam,John Tadross,Anthony Beucher,William H Colledge,Inês Cebola,Kevin G. Murphy,Irene Miguel-Aliaga,Giles S.H. Yeo,Waljit S. Dhillo,Bryn M. Owen
标识
DOI:10.1038/s41467-023-38618-y
摘要
Coupling the release of pituitary hormones to the developmental stage of the oocyte is essential for female fertility. It requires estrogen to restrain kisspeptin (KISS1)-neuron pulsatility in the arcuate hypothalamic nucleus, while also exerting a surge-like effect on KISS1-neuron activity in the AVPV hypothalamic nucleus. However, a mechanistic basis for this region-specific effect has remained elusive. Our genomic analysis in female mice demonstrate that some processes, such as restraint of KISS1-neuron activity in the arcuate nucleus, may be explained by region-specific estrogen receptor alpha (ERα) DNA binding at gene regulatory regions. Furthermore, we find that the Kiss1-locus is uniquely regulated in these hypothalamic nuclei, and that the nuclear receptor co-repressor NR0B1 (DAX1) restrains its transcription specifically in the arcuate nucleus. These studies provide mechanistic insight into how ERα may control the KISS1-neuron, and Kiss1 gene expression, to couple gonadotropin release to the developmental stage of the oocyte.
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