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

Abstract

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 Ki SS‐1 gene.

Results

Stimulation of the rHypoE8 cells with muscimol significantly increased the level of Ki SS‐1 messenger (m) RNA expression. The ability of muscimol to increase the level of Ki SS‐1 mRNA also was observed in the primary cultures of the neuronal cells from the fetal rat brains. The muscimol‐induced increase in Ki SS‐1 mRNA expression was completely inhibited in the presence of the GABA _A receptor antagonist. Although muscimol increased the expression of Ki SS‐1, the natural compound, GABA, failed to induce the expression of Ki SS‐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.