Nuclear Receptor LRH-1 Induces the Reproductive Neuropeptide Kisspeptin in the Hypothalamus

The differential expression and secretion of the neuropeptide kisspeptin from neurons in the arcuate (Arc) and anteroventral periventricular (AVPV) nuclei of the hypothalamus coordinate the temporal release of pituitary gonadotropins that control the female reproductive cycle. However, the molecular...

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Bibliographic Details
Published in:Molecular endocrinology (Baltimore, Md.) Md.), 2013-04, Vol.27 (4), p.598-605
Main Authors: Atkin, Stan D, Owen, Bryn M, Bookout, Angie L, Cravo, Roberta M, Lee, Charlotte, Elias, Carol F, Elmquist, Joel K, Kliewer, Steven A, Mangelsdorf, David J
Format: Article
Language:English
Subjects:
Animals
Arcuate Nucleus of Hypothalamus - metabolism
Female
Hypothalamus - metabolism
Kisspeptins - genetics
Kisspeptins - metabolism
Mice
Neurons - metabolism
Neuropeptides - genetics
Neuropeptides - metabolism
Original Research
Ovarian Follicle - metabolism
Ovarian Follicle - pathology
Receptors, Cytoplasmic and Nuclear - genetics
Receptors, Cytoplasmic and Nuclear - metabolism
Reproduction
RNA, Messenger - genetics
RNA, Messenger - metabolism
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Summary:The differential expression and secretion of the neuropeptide kisspeptin from neurons in the arcuate (Arc) and anteroventral periventricular (AVPV) nuclei of the hypothalamus coordinate the temporal release of pituitary gonadotropins that control the female reproductive cycle. However, the molecular basis for this differential regulation is incompletely understood. Here, we report that liver receptor homolog-1 (LRH-1), a member of the nuclear receptor superfamily, is expressed in kisspeptin neurons in the Arc but not in the AVPV in female mice. LRH-1 binds directly to the kisspeptin (Kiss1) promoter and stimulates Kiss1 transcription. Deletion of LRH-1 from kisspeptin neurons in mice decreased Kiss1 expression in the Arc, leading to reduced plasma FSH levels, dysregulated follicle maturation, and prolongation of the estrous cycle. Conversely, overexpression of LRH-1 in kisspeptin neurons increased Arc Kiss1 expression and plasma FSH concentrations. These studies provide a molecular basis for the differential regulation of basal kisspeptin expression in Arc and AVPV neurons and reveal a prominent role for LRH-1 in hypothalamus in regulating the female reproductive axis.
ISSN:0888-8809
1944-9917
DOI:10.1210/me.2012-1371