Journal
MOLECULAR ENDOCRINOLOGY
Volume 27, Issue 4, Pages 598-605Publisher
OXFORD UNIV PRESS INC
DOI: 10.1210/me.2012-1371
Keywords
NURSA Molecule Pages: Nuclear Receptors: LRH-1
Categories
Funding
- Howard Hughes Medical Institute
- National Institutes of Health [U19DK62434, GM007062, HD69702, U54-HD28934]
- Robert A. Welch Foundation [I-1275, I-1558]
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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. (Molecular Endocrinology 27:598-605, 2013)
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