Open AccessGamma‐aminobutyric acid A receptor agonist, muscimol, increases Ki SS ‐1 gene expression in hypothalamic cell models
Author(s) -
Kanasaki Haruhiko,
Tumurbaatar Tuvshintugs,
Oride Aki,
Hara Tomomi,
Okada Hiroe,
Kyo Satoru
Publication year - 2017
Publication title -
reproductive medicine and biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.005
H-Index - 22
eISSN - 1447-0578
pISSN - 1445-5781
DOI - 10.1002/rmb2.12061
Subject(s) - muscimol , agonist , medicine , endocrinology , receptor , gamma aminobutyric acid , gabaergic , chemistry , gonadotropin releasing hormone , gabaa receptor , gaba receptor , stimulation , biology , hormone , luteinizing hormone
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 ( rH ypoE8) 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 rH ypoE8 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 rH ypoE8 cells. Muscimol did not modulate gonadotropin‐releasing hormone expression in either the rH ypoE8 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.