Dax1 modulates ERα-dependent hypothalamic estrogen sensing in female mice.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 05 2023
29 05 2023
Historique:
received:
23
05
2022
accepted:
10
05
2023
medline:
31
5
2023
pubmed:
30
5
2023
entrez:
29
5
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37248237
doi: 10.1038/s41467-023-38618-y
pii: 10.1038/s41467-023-38618-y
pmc: PMC10227040
doi:
Substances chimiques
Estradiol
4TI98Z838E
Estrogen Receptor alpha
0
Estrogens
0
Kisspeptins
0
Nr0b1 protein, mouse
0
DAX-1 Orphan Nuclear Receptor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3076Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/S017593/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/W001497/1
Pays : United Kingdom
Organisme : British Heart Foundation
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_1102/3
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00014/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 105545/Z/14/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/W018934/1
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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