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ID 52807
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Author
Terasaka, Tomohiro
Tsukamoto, Naoko
Nakamura, Eri
Toma, Kishio
Ogura-Ochi, Kanako
Glidewell-Kenney, Christine
Lawson, Mark A.
Abstract
Reproduction is integrated by interaction of neural and hormonal signals converging on hypothalamic neurons for controlling gonadotropin-releasing hormone (GnRH). Kisspeptin, the peptide product of the kiss1 gene and the endogenous agonist for the GRP54 receptor, plays a key role in the regulation of GnRH secretion. In the present study, we investigated the interaction between kisspeptin, estrogen and BMPs in the regulation of GnRH production by using mouse hypothalamic GT1-7 cells. Treatment with kisspeptin increased GnRH mRNA expression and GnRH protein production in a concentration-dependent manner. The expression levels of kiss1 and GPR54 were not changed by kisspeptin stimulation. Kisspeptin induction of GnRH was suppressed by co-treatment with BMPs, with BMP-4 action being the most potent for suppressing the kisspeptin effect. The expression of kisspeptin receptor, GPR54, was suppressed by BMPs, and this effect was reversed in the presence of kisspeptin. It was also revealed that BMP-induced Smad1/5/8 phosphorylation and Id-1 expression were suppressed and inhibitory Smad6/7 was induced by kisspeptin. In addition, estrogen induced GPR54 expression, while kisspeptin increased the expression levels of ER alpha. and ER beta, suggesting that the actions of estrogen and kisspeptin are mutually enhanced in GT1-7 cells. Moreover, kisspeptin stimulated MAPKs and AKT signaling, and ERK signaling was functionally involved in the kisspeptin-induced GnRH expression. BMP-4 was found to suppress kisspeptin-induced GnRH expression by reducing ERK signaling activity. Collectively, the results indicate that the axis of kisspeptin-induced GnRH production is bi-directionally controlled, being augmented by an interaction between ER alpha/beta and GPR54 signaling and suppressed by BMP-4 action in GT1-7 neuron cells.
Keywords
BMP
Estradiol
GnRH
GPR54
Kisspeptin
MAPK
Published Date
2013-12-05
Publication Title
Molecular and Cellular Endocrinology
Volume
volume381
Issue
issue1-2
Start Page
8
End Page
15
ISSN
0303-7207
Content Type
Journal Article
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/52532
language
英語
Copyright Holders
(C) 2013 Elsevier Ireland Ltd. All rights reserved.
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author
Refereed
True
DOI
Web of Sience KeyUT