SFEBES2018 Poster Presentations Reproduction (23 abstracts)
Dax1 controls female fertility as a hypothalamic rheostat of estrogen receptor-alpha
Isabel Fernandes Freitas 1 , Stephen Manchishi 2 , William Colledge 2 , Waljit Dhillo 1 & Bryn Owen 1
1Section of Investigative Medicine, Imperial College London, London, UK; 2Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, UK.
Coupling the release of pituitary hormones to the developmental stage of the oocyte is essential for female fertility. It requires estrogen to have simultaneous positive and negative feedback effects on spatially-distinct regions of the hypothalamus. However, the mechanistic basis for this differential effect is not known. We have found that negative-feedback is mediated by the nuclear receptor Dax1, which is present in the arcuate hypothalamic nucleus and serves as a ligand-dependent repressor of ERa transcriptional activity. It decreases follicle stimulating hormone release in response to rising ovarian estrogen production. Concordantly, mice lacking Dax1 in cells expressing the reproductive-neuropeptide kisspeptin have abnormal estrogen-stimulated gonadotropin secretion and fail to cycle normally. As such, the interaction between Dax1 and ERa in the arcuate hypothalamus explains the paradoxical observation of hypothalamic estradiol negative-feedback.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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