Biomaterial Database

Dax1 modulates ERα-dependent hypothalamic estrogen sensing in female mice. 2023

Jose M Ramos-Pittol, and Isabel Fernandes-Freitas, and Alexandra Milona, and Stephen M Manchishi, and Kara Rainbow, and Brian Y H Lam, and John A Tadross, and Anthony Beucher, and William H Colledge, and Inês Cebola, and Kevin G Murphy, and Irene Miguel-Aliaga, and Giles S H Yeo, and Waljit S Dhillo, and Bryn M Owen

Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, 6020, Austria.

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.

UI	MeSH Term	Description	Entries
D007031	Hypothalamus	Ventral part of the DIENCEPHALON extending from the region of the OPTIC CHIASM to the caudal border of the MAMMILLARY BODIES and forming the inferior and lateral walls of the THIRD VENTRICLE.	Lamina Terminalis,Preoptico-Hypothalamic Area,Area, Preoptico-Hypothalamic,Areas, Preoptico-Hypothalamic,Preoptico Hypothalamic Area,Preoptico-Hypothalamic Areas
D004958	Estradiol	The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.	17 beta-Estradiol,Estradiol-17 beta,Oestradiol,17 beta-Oestradiol,Aerodiol,Delestrogen,Estrace,Estraderm TTS,Estradiol Anhydrous,Estradiol Hemihydrate,Estradiol Hemihydrate, (17 alpha)-Isomer,Estradiol Monohydrate,Estradiol Valerate,Estradiol Valeriante,Estradiol, (+-)-Isomer,Estradiol, (-)-Isomer,Estradiol, (16 alpha,17 alpha)-Isomer,Estradiol, (16 alpha,17 beta)-Isomer,Estradiol, (17-alpha)-Isomer,Estradiol, (8 alpha,17 beta)-(+-)-Isomer,Estradiol, (8 alpha,17 beta)-Isomer,Estradiol, (9 beta,17 alpha)-Isomer,Estradiol, (9 beta,17 beta)-Isomer,Estradiol, Monosodium Salt,Estradiol, Sodium Salt,Estradiol-17 alpha,Estradiol-17beta,Ovocyclin,Progynon-Depot,Progynova,Vivelle,17 beta Estradiol,17 beta Oestradiol,Estradiol 17 alpha,Estradiol 17 beta,Estradiol 17beta,Progynon Depot
D004967	Estrogens	Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.	Estrogen,Estrogen Effect,Estrogen Effects,Estrogen Receptor Agonists,Estrogenic Agents,Estrogenic Compounds,Estrogenic Effect,Estrogenic Effects,Agents, Estrogenic,Agonists, Estrogen Receptor,Compounds, Estrogenic,Effects, Estrogen,Effects, Estrogenic,Receptor Agonists, Estrogen
D005260	Female		Females
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001111	Arcuate Nucleus of Hypothalamus	A nucleus located in the middle hypothalamus in the most ventral part of the THIRD VENTRICLE near the entrance of the infundibular recess. Its small cells are in close contact with the EPENDYMA.	Arcuate Nucleus,Infundibular Nucleus,Hypothalamus Arcuate Nucleus,Nucleus, Arcuate,Nucleus, Infundibular
D047628	Estrogen Receptor alpha	One of the ESTROGEN RECEPTORS that has marked affinity for ESTRADIOL. Its expression and function differs from, and in some ways opposes, ESTROGEN RECEPTOR BETA.	ERalpha,Estradiol Receptor alpha,Estrogen Receptor 1,Estrogen Receptors alpha,Receptor alpha, Estrogen,Receptor alpha, Estradiol,alpha, Estradiol Receptor
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D057137	DAX-1 Orphan Nuclear Receptor	An orphan nuclear receptor that is implicated in regulation of steroidogenic pathways. It is unlike most orphan nuclear receptors in that it appears to lack an essential DNA-binding domain and instead acts as a transcriptional co-repressor. Mutations in the gene Dax-1 cause congenital adrenal hypoplasia.	DSS-AHC Critical Region on the X Chromosome, Gene 1 Protein,NR0B1 Protein,Nuclear Receptor 0B1,Nuclear Receptor DAX-1,Nuclear Receptor NR0B1,Nuclear Receptor Subfamily 0, Group B, Member 1,DAX 1 Orphan Nuclear Receptor,DSS AHC Critical Region on the X Chromosome, Gene 1 Protein,Nuclear Receptor DAX 1
D059648	Kisspeptins	Intercellular signaling peptides that were originally characterized by their ability to suppress NEOPLASM METASTASIS. Kisspeptins have since been found to play an important role in the neuroendocrine regulation of REPRODUCTION.	Kisspeptin,Metastin,KiSS-1 Metastasis Suppressor,Kisspeptin-1,Metastasis Suppressor KiSS-1,Metastins,KiSS 1 Metastasis Suppressor,KiSS-1, Metastasis Suppressor,Kisspeptin 1,Metastasis Suppressor KiSS 1,Metastasis Suppressor, KiSS-1