Gamma-aminobutyric acid A receptor agonist, muscimol, increases KiSS-1 gene expression in hypothalamic cell models

Reproductive medicine and biology

article

Haruhiko Kanasaki¹  Tuvshintugs Tumurbaatar¹  Aki Oride¹  Tomomi Hara¹  Hiroe Okada¹  Satoru Kyo¹ 

[1]Department of Obstetrics and Gynecology, Shimane University School of Medicine

关键词: gamma-aminobutyric acidA receptor;    gonadotropin-releasing hormone;    hypothalamus;    kisspeptin;    muscimol;   

DOI  :  10.1002/rmb2.12061

学科分类：工业工程学

来源: Wiley

【 摘 要 】

Purpose Accumulating evidence indicates that hypothalamic kisspeptin plays a pivotal role in the regulation of the hypothalamic–pituitary–gonadal (HPG) axis. In this study, the direct action of the gamma-aminobutyric acid (GABA) A receptor agonist on kisspeptin-expressing neuronal cells was examined. Methods A hypothalamic cell model of rat hypothalamic cell line R8 (rHypoE8) cells and primary cultures of neuronal cells from fetal rat brains were stimulated with a potent and selective GABA A receptor agonist, muscimol, to determine the expression of the KiSS-1 gene. Results Stimulation of the rHypoE8 cells with muscimol significantly increased the level of KiSS-1 messenger (m)RNA expression. The ability of muscimol to increase the level of KiSS-1 mRNA also was observed in the primary cultures of the neuronal cells from the fetal rat brains. The muscimol-induced increase in KiSS-1 mRNA expression was completely inhibited in the presence of the GABA A receptor antagonist. Although muscimol increased the expression of KiSS-1, the natural compound, GABA, failed to induce the expression of KiSS-1 in the rHypoE8 cells. Muscimol did not modulate gonadotropin-releasing hormone expression in either the rHypoE8 cells or the primary cultures of the fetal rat brains. Conclusions This study's observations suggest that the activation of the GABA A receptor modulates the HPG axis by increasing kisspeptin expression in the hypothalamic neurons.

【 授权许可】

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