Kanasaki Haruhiko, Tselmeg Mijiddorj, Oride Aki, Sukhbaatar Unurjargal, Hara Tomomi, Kyo Satoru
a Shimane University , Izumo , Japan.
Gynecol Endocrinol. 2017 Sep;33(9):721-727. doi: 10.1080/09513590.2017.1318277. Epub 2017 Apr 27.
Hypothalamic kisspeptin is integral to the hypothalamic-pituitary-gonadal axis by stimulating gonadotropin-releasing hormone (GnRH) release. GnRH is released from the hypothalamus in a pulsatile manner and determines the output of the gonadotropins. However, the effect of kisspeptin on GnRH-secreting cells remains unknown. In an experiment using static cultures of GT1-7 cells, kisspeptin did not significantly increase GnRH mRNA expression. However, when kisspeptin was administered to the cells in a pulsatile manner, GnRH mRNA expression was significantly increased. Primary cultures of fetal rat brain containing GnRH-expressing neurons responded to kisspeptin and increased GnRH mRNA expression by 1.65 ± 0.27-fold in the static condition. When cells were stimulated with kisspeptin in a pulsatile manner, GnRH mRNA expression was increased by up to 2.40 ± 0.21-fold. In perifused GT1-7 cells, pulsatile, but not continuous kisspeptin stimulation, effectively stimulated GnRH mRNA expression. To assess the level of stimulation of GnRH neurons by kisspeptin, the expression of c-fos was examined. In GT1-7 cells, kisspeptin stimulation in the static condition failed to increase c-fos mRNA expression. However, pulsatile kisspeptin stimulation increased c-fos mRNA by 2.31 ± 0.47-fold. Similar to the phenomenon observed in GT1-7 cells, pulsatile, but not static, kisspeptin stimulation significantly increased c-fos mRNA expression in the primary cultures of fetal rat brain. These observations suggest that pulsatile kisspeptin more effectively stimulates GnRH-producing cells to increase the production of GnRH.
下丘脑的亲吻素通过刺激促性腺激素释放激素(GnRH)的释放,对下丘脑-垂体-性腺轴至关重要。GnRH以脉冲方式从下丘脑释放,并决定促性腺激素的输出。然而,亲吻素对GnRH分泌细胞的作用仍不清楚。在一项使用GT1-7细胞静态培养的实验中,亲吻素并未显著增加GnRH mRNA的表达。然而,当以脉冲方式向细胞施用亲吻素时,GnRH mRNA的表达显著增加。含有表达GnRH神经元的胎鼠脑原代培养物对亲吻素产生反应,在静态条件下GnRH mRNA表达增加了1.65±0.27倍。当以脉冲方式用亲吻素刺激细胞时,GnRH mRNA表达增加至2.40±0.21倍。在灌流的GT1-7细胞中,脉冲式而非连续的亲吻素刺激有效地刺激了GnRH mRNA的表达。为了评估亲吻素对GnRH神经元的刺激水平,检测了c-fos的表达。在GT1-7细胞中,静态条件下的亲吻素刺激未能增加c-fos mRNA的表达。然而,脉冲式亲吻素刺激使c-fos mRNA增加了2.31±0.47倍。与在GT1-7细胞中观察到的现象类似,脉冲式而非静态的亲吻素刺激在胎鼠脑原代培养物中显著增加了c-fos mRNA的表达。这些观察结果表明,脉冲式亲吻素能更有效地刺激GnRH产生细胞增加GnRH的产生。