Son You Lee, Ubuka Takayoshi, Soga Tomoko, Yamamoto Kazutoshi, Bentley George E, Tsutsui Kazuyoshi
Laboratory of Integrative Brain Sciences, Department of Biology, Center for Medical Life Science of Waseda University, Tokyo, Japan;
Laboratory of Integrative Brain Sciences, Department of Biology, Center for Medical Life Science of Waseda University, Tokyo, Japan; Brain Research Institute, School of Medicine and Health Sciences, Monash University, Sunway, Malaysia; and.
FASEB J. 2016 Jun;30(6):2198-210. doi: 10.1096/fj.201500055. Epub 2016 Feb 29.
Gonadotropin-inhibitory hormone (GnIH) acts as a negative regulator of reproduction by acting on gonadotropes and gonadotropin-releasing hormone (GnRH) neurons. Despite its functional significance, the molecular mechanism of GnIH action in the target cells has not been fully elucidated. To expand our previous study on GnIH actions in gonadotropes, we investigated the potential signal transduction pathway that conveys the inhibitory action of GnIH in GnRH neurons by using the GnRH neuronal cell line, GT1-7. We examined whether GnIH inhibits the action of kisspeptin and vasoactive intestinal polypeptide (VIP), positive regulators of GnRH neurons. Although GnIH significantly suppressed the stimulatory effect of kisspeptin on GnRH release in hypothalamic culture, GnIH had no inhibitory effect on kisspeptin stimulation of serum response element and nuclear factor of activated T-cell response element activities and ERK phosphorylation, indicating that GnIH may not directly inhibit kisspeptin signaling in GnRH neurons. On the contrary, GnIH effectively eliminated the stimulatory effect of VIP on p38 and ERK phosphorylation, c-Fos mRNA expression, and GnRH release. The use of pharmacological modulators strongly demonstrated the specific inhibitory action of GnIH on the adenylate cyclase/cAMP/protein kinase A pathway, suggesting a common inhibitory mechanism of GnIH action in GnRH neurons and gonadotropes.-Son, Y. L., Ubuka, T., Soga, T., Yamamoto, K., Bentley, G. E., Tsutsui, K. Inhibitory action of gonadotropin-inhibitory hormone on the signaling pathways induced by kisspeptin and vasoactive intestinal polypeptide in GnRH neuronal cell line, GT1-7.
促性腺激素抑制激素（GnIH）通过作用于促性腺激素细胞和促性腺激素释放激素（GnRH）神经元，发挥生殖负调节因子的作用。尽管其功能具有重要意义，但GnIH在靶细胞中的分子作用机制尚未完全阐明。为了扩展我们之前关于GnIH在促性腺激素细胞中作用的研究，我们利用GnRH神经元细胞系GT1-7，研究了传递GnIH在GnRH神经元中抑制作用的潜在信号转导途径。我们检测了GnIH是否抑制GnRH神经元的正向调节因子—— kisspeptin和血管活性肠肽（VIP）的作用。尽管GnIH显著抑制了下丘脑培养物中kisspeptin对GnRH释放的刺激作用，但GnIH对kisspeptin刺激血清反应元件和活化T细胞反应元件活性以及ERK磷酸化没有抑制作用，这表明GnIH可能不会直接抑制GnRH神经元中的kisspeptin信号传导。相反，GnIH有效消除了VIP对p38和ERK磷酸化、c-Fos mRNA表达以及GnRH释放的刺激作用。药理学调节剂的使用有力地证明了GnIH对腺苷酸环化酶/cAMP/蛋白激酶A途径的特异性抑制作用，提示GnIH在GnRH神经元和促性腺激素细胞中作用的共同抑制机制。- 孙，Y. L.，宇部，T.，曾我部，T.，山本，K.，本特利，G. E.，津木井，K. 促性腺激素抑制激素对GnRH神经元细胞系GT1-7中kisspeptin和血管活性肠肽诱导的信号通路的抑制作用
