SFEBES2022 Poster Presentations Reproductive Endocrinology (36 abstracts)
Identification of a transcription factor that modulates ERα-Dependent Hypothalamic Estrogen Sensing
Isabel Fernandes-Freitas 1 , Alexandra Milona 1 , Jose Ramos-Pittol 2 , Stephen Manchishi 3 , Kara Rainbow 3 , Brian Lam 3 , John Tadross 3 , Anthony Beucher 1 , William Colledge 3 , Inês Cebola 1 , Kevin Murphy 1 , Irene Miguel-Aliaga 4 , Giles Yeo 3 , Waljit Dhillo 1 & Bryn Owen 1
1Imperial College, London, United Kingdom; 2University of Innsbruck, Innsbruck, Austria; 3Cambridge University, Cambridge, United Kingdom; 4MRC LMS, London, United Kingdom
Coupling the release of pituitary hormones to the developmental stage of the oocyte is essential for female fertility. It is thought to require estrogen to have simultaneous positive and negative feedback effects on two spatially-distinct regions of the hypothalamus, the arcuate nucleus and ‘AVPV’ nucleus. However, the mechanistic basis for this differential effect is not known. Therefore, we mapped the genomic binding of the estrogen receptor alpha (ERα) in both locations under estrogen stimulation. We found differences that were consistent with the hypothesis that region-specific transcription factors modulate ERα activity. Indeed, we went on to find that a specific transcription factor is present exclusively in the arcuate hypothalamic nucleus and serves as a ligand-dependent repressor of the Kiss1-gene, which is essential for fertility. We generated mice lacking this transcription factor in Kisspeptin-neurons and show that these fail to appropriately modulate hormone secretion. Concordantly, these mice fail to cycle normally, and have impaired fertility. Together, these findings have implications for our understanding of how hypothalamic estrogen signalling translates to appropriate gonadotropin release and the maintenance of fertility.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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