Dax1 modulates ERα-dependent hypothalamic estrogen sensing in female mice.

Autor: Ramos-Pittol JM; Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, 6020, Austria., Fernandes-Freitas I; Section of Investigative Medicine, Imperial College London, London, United Kingdom., Milona A; Institute of Clinical Sciences, Imperial College London, London, United Kingdom., Manchishi SM; Department of Physiology, Development, and Neuroscience, Cambridge University, Cambridge, United Kingdom., Rainbow K; Medical Research Council Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, Cambridge University, Cambridge, United Kingdom., Lam BYH; Medical Research Council Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, Cambridge University, Cambridge, United Kingdom., Tadross JA; Medical Research Council Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, Cambridge University, Cambridge, United Kingdom.; Department of Histopathology and East Midlands & East of England Genomic Laboratory Hub, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Beucher A; Section of Genetics and Genomics, Imperial College London, London, United Kingdom., Colledge WH; Department of Physiology, Development, and Neuroscience, Cambridge University, Cambridge, United Kingdom., Cebola I; Section of Genetics and Genomics, Imperial College London, London, United Kingdom., Murphy KG; Section of Investigative Medicine, Imperial College London, London, United Kingdom., Miguel-Aliaga I; Institute of Clinical Sciences, Imperial College London, London, United Kingdom.; MRC London Institute of Medical Sciences, London, United Kingdom., Yeo GSH; Medical Research Council Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, Cambridge University, Cambridge, United Kingdom., Dhillo WS; Section of Investigative Medicine, Imperial College London, London, United Kingdom. w.dhillo@imperial.ac.uk., Owen BM; Section of Investigative Medicine, Imperial College London, London, United Kingdom. bryn.owen05@imperial.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 May 29; Vol. 14 (1), pp. 3076. Date of Electronic Publication: 2023 May 29.
DOI: 10.1038/s41467-023-38618-y
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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