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1 April 2017 GLP-1 increases Kiss-1 mRNA expression in kisspeptin-expressing neuronal cells
Aki Oride, Haruhiko Kanasaki, Tselmeg Mijiddorj, Unurjargal Sukhbaatar, Tomomi Hara, Tuvshintugs Tumurbaatar, Satoru Kyo
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Abstract

Feeding-related metabolic factors exert regulatory influences on the hypothalamic–pituitary–gonadal axis. Glucagon-like peptide-1 (GLP-1) is an anorexigenic hormone synthesized from the ileum in response to food intake. The purpose of this study was to examine the direct effect of GLP-1 on hypothalamic kisspeptin and gonadotropin-releasing hormone (GnRH) expression using the rat clonal hypothalamic cell line rHypoE-8. GLP-1 significantly increased Kiss-1 mRNA expression in rHypoE-8 cells up to 1.94 ± 0.22-fold. This effect of GLP-1 on Kiss-1 gene expression was also observed in GT1–7 GnRH-producing neurons and in primary cultures of fetal rat brain. GLP-1 increased cAMP-mediated signaling, as determined by cAMP response element activity assays, but failed to activate extracellular signal-regulated kinase pathways. Another anorexigenic factor, leptin, similarly increased Kiss-1 mRNA levels up to 1.34 ± 0.08-fold in rHypoE-8 cells. However, combined treatment with GLP-1 and leptin failed to potentiate their individual effects on Kiss-1 mRNA expression. Gnrh mRNA expression was not significantly increased by GLP-1 stimulation in rHypoE-8, but kisspeptin significantly stimulated the expression of Gnrh mRNA in these cells. Our current observations suggest that the anorexigenic peptide GLP-1 directly regulates Kiss-1 mRNA expression in these hypothalamic cell lines and in neuronal cells of fetal rat brain and affects the expression of Gnrh mRNA.

Summary Sentence

Anorexigenic peptide GLP-1 directly regulates Kiss-1 mRNA expression in thypothalamic cell lines and affects the expression of Gnrh mRNA.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Aki Oride, Haruhiko Kanasaki, Tselmeg Mijiddorj, Unurjargal Sukhbaatar, Tomomi Hara, Tuvshintugs Tumurbaatar, and Satoru Kyo "GLP-1 increases Kiss-1 mRNA expression in kisspeptin-expressing neuronal cells," Biology of Reproduction 97(2), 240-248, (1 April 2017). https://doi.org/10.1093/biolre/iox0871
Received: 25 March 2017; Accepted: 4 August 2017; Published: 1 April 2017
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