Nature communications · 2023
Dax1 modulates ERα-dependent hypothalamic estrogen sensing in female mice.
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Ramos-Pittol Jose M, Fernandes-Freitas Isabel, Milona Alexandra, Manchishi Stephen M, Rainbow Kara, Lam Brian Y H, Tadross John A, Beucher Anthony, Colledge William H, Cebola Inês, Murphy Kevin G, Miguel-Aliaga Irene, Yeo Giles S H, Dhillo Waljit S, Owen Bryn M
Аннотация
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.