Cloning of the factors determining specific production of GH in somatotrophs and their pathophysiological significance

生长激素细胞GH特异性产生因子的克隆及其病理生理意义

• 批准号: 17590962
• 负责人: OKIMURA Yasuhiko
• 金额: $ 2.24万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590962/
• 关键词: growth hormone; LCR of GH gene; ES cells; LCR; 成長ホルモン遺伝子; RNAi library

Pit-1 is a pituitary specific transcription factor that stimulates growth hormone (GH), prolactin (PRL) and TSH-β gene expression. However it is difficult to explain cell-specific expression of GH, PRL and TSH-β since they are produced in different cells. Although locus control region (LCR) of GH gene is important to determine somatotroph-specific expression of GH, it is unknown what mechanism regulates cell-specific expression of GH. To clarify the mechanism, we tried to find factors that bind to the LCR using cell sorting of pituitary cells containing LCR-GH-GFP reporter in genome DNA and RNA interference library. Unfortunately we cannot obtain the factors until now. However the significance of LCR in cell differentiation has been clarified in our study. We established ES cells that contain LCR-GH-GFP gene in their genomes. GFP expression was parallel to GH production in the ES cells during differentiation to somatotrophs. GFP expression was higher in the cells containing LCR-GH-GFP gene than the cells with GH-GFP gene. Next, we tested the functions of hormones, growth factors and cytokines to stimulate differentiation to somatotrophs and unexpectedly found LIF was a potent factor.

PIT-1是一种垂体特异性转录因子，可刺激生长激素(GH)、催乳素(PRL)和促甲状腺激素-β基因的表达。然而，由于生长激素、催乳素和促甲状腺激素-β在不同的细胞中产生，因此很难解释它们的细胞特异性表达。虽然生长激素基因的位点控制区(LCR)对于决定生长激素的生长激素特异性表达是重要的，但目前还不清楚是什么机制调节了生长激素的细胞特异性表达。为了阐明LCR的作用机制，我们试图通过对基因组DNA和RNA干扰文库中含有LCR-GH-GFP报告的垂体细胞进行细胞分选来寻找与LCR结合的因子。不幸的是，到目前为止我们还不能获得这些因素。然而，在我们的研究中，LCR在细胞分化中的意义已经被阐明。我们建立了基因组中含有LCR-GH-GFP基因的ES细胞。在ES细胞向生长激素细胞分化的过程中，GFP的表达与GH的产生是平行的。携带LCR-GH-GFP基因的细胞GFP表达高于携带GH-GFP基因的细胞。接下来，我们测试了激素、生长因子和细胞因子刺激向生长激素细胞分化的功能，意外地发现LIF是一个强有力的因素。

项目成果

The N131S Mutation in the von Hippel-Lindau Gene in a Japanese Family with Pheochromocytoma and Hemangioblastomas.

日本嗜铬细胞瘤和血管母细胞瘤家族中 von Hippel-Lindau 基因的 N131S 突变。

• 发表时间: 2006
• 期刊: Endocrine Journal 53(6)
• 作者: Yamada S;(他8名;Miki T;は7番目);N. Kaji;Mari Imanaka
• 通讯作者: Mari Imanaka

Growth hormone reverses nonalcoholic steatohepatitis in a patient with adult growth hormone deficiency

• DOI: 10.1053/j.gastro.2006.12.024
• 发表时间: 2007-03-01
• 期刊: GASTROENTEROLOGY
• 影响因子: 29.4
• 作者: Takahashi, Yutaka;Iida, Keiji;Chihara, Kazuo
• 通讯作者: Chihara, Kazuo

Gene expression profile in the heart of spontaneous dwarf rat: In vivo effects of growth hormone.

自发性侏儒大鼠心脏中的基因表达谱：生长激素的体内作用。

• 发表时间: 2006
• 期刊: Biochemical and Biophysical Research Communications 341
• 作者: Fujimoto W;Shiuchi T;Miki T;(他7名);Shiro Yositioka
• 通讯作者: Shiro Yositioka

A novel mutation in the von Hippel-Lindau tumor suppressor gene identified in a Japanese family with pheochromocytoma and hepatic hemangioma

在一个患有嗜铬细胞瘤和肝血管瘤的日本家族中发现了 von Hippel-Lindau 肿瘤抑制基因的新突变

• 发表时间: 2006
• 期刊: Intern Med 45・5
• 作者: Dai;G;Yamamoto D;Imanaka M;Takahashi K
• 通讯作者: Takahashi K

Neither intravenous nor intracerebroventricular administration of obestatin affects the secretion of GH, PRL, TSH and ACTH in rats

• DOI: 10.1016/j.regpep.2006.09.001
• 发表时间: 2007-02
• 期刊: Regulatory Peptides
• 作者: Daisuke Yamamoto;Nobuko Ikeshita;Rie Daito;E. Herningtyas;Keizo Toda;Kentaro Takahashi;K. Iida