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The role of hypothalamic neuropeptides in the regulation of gonadotropins

下丘脑神经肽在促性腺激素调节中的作用

基本信息

批准号：
20591916
负责人：
MIYAZAKI Kohji
金额：
$ 2.83万
依托单位：
Shimane University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591916/
关键词：
ゴナドトロピン下垂体 GnRH ERK MKP PACAP

项目摘要

In this present study, we examined the expression of MKP-1 by GnRH stimulation and investigated the possible role of MKP-1 on gonadotropin gene expression using gonadotroph cell line, LβT2 cells. MKP-1 expression was remarkably increased 60minutes after GnRH stimulation and ERK activation was gradually decreased after 60minutes. GnRH-induced ERK activation was completely inhibited in the presence of U0126, a MEK inhibitor, whereas GnRH-induced MKP-1 expression was partially inhibited by U0126. GnRH-induced MKP-1 induction was inhibited by dose dependently in the presence of triptolide, a diterpenoid triepoxide. On the other hand, ERK activation was potentiated at this time by this compound. U0126 prevented GnRH-stimulated gonadotropin LHβ and FSHβ subunit promoter activity by dose dependently. Whereas, GnRH-stimulated LHb and FSHb promoter activities were almost completely inhibited by triptolide. In addition, under pulsatile GnRH stimulation, MKP-1 expression was observed in high frequency GnRH pulse which preferentially increase LHb, but not in low frequency pulse under which FSHb preferentially increased. Our study demonstrated that MKP-1 induced by GnRH works not only as an ERK-inactivating phosphatase, but also as an important mediator which control gonadotoropin subunit gene expressions.

在本研究中，我们检测了MKP-1的表达由GnRH刺激，并探讨了MKP-1对促性腺激素基因表达的可能作用，使用促性腺激素细胞系，LβT2细胞。MKP-1表达在GnRH刺激后60分钟显著增加，ERK激活在60分钟后逐渐减少。GnRH诱导的ERK激活在MEK抑制剂U 0126的存在下被完全抑制，而GnRH诱导的MKP-1表达被U 0126部分抑制。GnRH诱导的MKP-1诱导在雷公藤甲素（一种二萜类三环氧化物）存在下受到剂量依赖性抑制。另一方面，ERK激活在此时被该化合物增强。U 0126剂量依赖性地抑制GnRH刺激的促性腺激素LHβ和FSHβ亚基启动子活性。雷公藤内酯醇几乎完全抑制GnRH刺激的LHb和FSHb启动子活性。此外，在脉冲式GnRH刺激下，MKP-1在高频GnRH脉冲下表达，其优先增加LHb，而在低频脉冲下不表达，其优先增加FSHb。我们的研究表明，GnRH诱导的MKP-1不仅作为ERK失活的磷酸酶发挥作用，而且作为一种重要的调节剂调控促性腺激素亚单位基因的表达。