Study for physiological function of metastin/kisspeptin with special reference to reproduction.

研究转移蛋白/Kisspeptin 的生理功能，特别是生殖方面的功能。

• 批准号: 19390252
• 负责人: INOUE Kinji
• 金额: $ 10.57万
• 依托单位: Saitama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19390252/
• 关键词: メタスチン; キスペプチン; 生殖制御; 時計遺伝子; がん転移; 前腹側室周囲核(AVPV); 視床下部弓状核(ARC); エストロゲン; LHサージ; アポトーシス; Metastin; AVPV; 弓城核; GABA; 転移; 末梢組織; 脳内分布

We previously found that metastin/kisspeptin is produced in anteroventral periventricular nucleus(AVPV) and arcuate nucleus(Arc.) in the hypothalamus. It is also revealed that metastin gene (kiss-1) expression in AVPV is positively and Arc is negatively regulated by estrogen and may be involved in ovulation and gonadal development through the surge or pulse mode release of GnRH/LH. In this study we found a clock gene which regulates metastin gene expression. The clock gene (Dbp) shows not only additive effects with E2 and it's nuclear receptor ERa on the expression of metastin, but correlation of spatio-temporal expression pattern between Dbp and metastin. These results strongly suggest Dbp is key regulator, which set a time of LH surge.In this study we also performed immunocytochemical study for metastin and GnRH neurons and found that metastin and GnRH nerve fibers closely contacted at median eminence, which strongly suggest that metastin may regulate GnRH neurons in median eminence. On the other hand, metastin is found as a peptide which suppresses metastasis of cancer cells however, the effect of metastin on metastasis is not well studied. In this study we found that metastin activates ERK1/2 gene in many kind of cancer cells. We also found that metastin has no effect on the cancer cell proliferation and apoptosis however, it inhibited migration of a mammary carcinoma and a lung carcinoma cells.

我们之前发现转移蛋白/kisspeptin在下丘脑腹侧脑室周围核（AVPV）和弓形核（Arc）中产生。研究还发现，转移酶基因（kiss-1）在AVPV中的表达呈阳性，而Arc受雌激素的负向调控，可能通过GnRH/LH的激增或脉冲释放参与排卵和性腺发育。在这项研究中，我们发现了一个调节转移蛋白基因表达的时钟基因。时钟基因（Dbp）不仅与E2及其核受体ERa对转移蛋白的表达有加性作用，而且Dbp与转移蛋白的时空表达模式存在相关性。这些结果强烈表明舒张压是关键的调节因子，它设定了LH激增的时间。在本研究中，我们还对转抑素和GnRH神经元进行了免疫细胞化学研究，发现转抑素和GnRH神经纤维在正中隆起处紧密接触，这强烈提示转抑素可能调节正中隆起的GnRH神经元。另一方面，转移素是一种抑制癌细胞转移的肽，但其对癌细胞转移的影响尚不清楚。在本研究中，我们发现转移汀在多种癌细胞中激活ERK1/2基因。我们还发现转移汀对癌细胞的增殖和凋亡没有影响，但对乳腺癌和肺癌细胞的迁移有抑制作用。

项目成果

Involvement of anteroventral periventricular metastin/kisspeptin neurons in estrogen positive feedback action on luteinizing hormone release in female rats

• DOI: 10.1262/jrd.18146
• 发表时间: 2007-04-01
• 期刊: JOURNAL OF REPRODUCTION AND DEVELOPMENT
• 影响因子: 1.8
• 作者: Adachi, Sachika;Yamada, Shunji;Maeda, Kei-Ichiro
• 通讯作者: Maeda, Kei-Ichiro

下垂体前葉細胞の増殖と分化の新たな展開

垂体前叶细胞增殖和分化的新进展

• 发表时间: 2009
• 作者: N. Arai;H. Masuzaki;T. Tanaka;T. Ishii;S. Yasue;N. Kobayashi;T. Tomita;M. Noguchi;T. Kusakabe;H. Tanioka;H. Hige;F. Miyanaga;J. Fujikura;K. Ebihara;M. Hirata;K. Hosoda;H. Sawai;Y. Minokoshi;K. Nakao;井上金治
• 通讯作者: 井上金治

Serum levels of nicotinamide N-methyltransferase in patients with lung cancer

• DOI: 10.1007/s00432-009-0563-y
• 发表时间: 2009-09-01
• 期刊: JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
• 影响因子: 3.6
• 作者: Tomida, Mikio;Mikami, Iwao;Akiyama, Hirohiko
• 通讯作者: Akiyama, Hirohiko

Stress Response of Prolactin-Releasing Peptide Knockout Mice as to Glucocorticoid Secretion

• DOI: 10.1111/j.1365-2826.2010.01993.x
• 发表时间: 2010-06-01
• 期刊: JOURNAL OF NEUROENDOCRINOLOGY
• 影响因子: 3.2
• 作者: Mochiduki, A.;Takeda, T.;Inoue, K.
• 通讯作者: Inoue, K.