First Author | Ramos-Pittol JM | Year | 2023 |
Journal | Nat Commun | Volume | 14 |
Issue | 1 | Pages | 3076 |
PubMed ID | 37248237 | Mgi Jnum | J:341011 |
Mgi Id | MGI:7487434 | Doi | 10.1038/s41467-023-38618-y |
Citation | Ramos-Pittol JM, et al. (2023) Dax1 modulates ERalpha-dependent hypothalamic estrogen sensing in female mice. Nat Commun 14(1):3076 |
abstractText | 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 (ERalpha) 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 ERalpha may control the KISS1-neuron, and Kiss1 gene expression, to couple gonadotropin release to the developmental stage of the oocyte. |