Nuclear receptor LRH-1 induces the reproductive neuropeptide kisspeptin in the hypothalamus

Stan D. Atkin, Bryn M. Owen, Angie L. Bookout, Roberta M. Cravo, Charlotte Lee, Carol F. Elias, Joel K. Elmquist, Steven A. Kliewer, David J. Mangelsdorf

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)598-605
Number of pages8
JournalMolecular Endocrinology
Volume27
Issue number4
DOIs
StatePublished - Apr 1 2013

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Kisspeptins
Cytoplasmic and Nuclear Receptors
Neuropeptides
Hypothalamus
Liver
Neurons
Pituitary Gonadotropins
Anterior Hypothalamus
Estrous Cycle

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Nuclear receptor LRH-1 induces the reproductive neuropeptide kisspeptin in the hypothalamus. / 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.

In: Molecular Endocrinology, Vol. 27, No. 4, 01.04.2013, p. 598-605.

Research output: Contribution to journalArticle

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. / Nuclear receptor LRH-1 induces the reproductive neuropeptide kisspeptin in the hypothalamus. In: Molecular Endocrinology. 2013 ; Vol. 27, No. 4. pp. 598-605.
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