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Physiological and pathological significance of mPOU, anovel transcription factor that amplifies prolactin gene expression

mPOU（一种放大催乳素基因表达的新型转录因子）的生理和病理意义

基本信息

批准号：
12671085
负责人：
OKIMURA Yasuhiko
金额：
$ 2.18万
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：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671085/
关键词：
prolactin pituitary transcription factor mPOU pituitary tumor Pit-1 ノックアウトマウス PRL

项目摘要

We previously cloned a transcription factor, mPOU, which binds pit-1 binding DNA elements of PRL gene, from human pituitary DNA library. To clarify physiological and pathological significance, we first examined the effect of mPOU on the gene expressions regulated by Pit-1 in transient expressions and luciferase reporter gene systems, mPOU and Pit-1 synergistically activated the prolactin (PRL) reporter gene expression, mPOU and pit-1 additively stimulated growth hormone (GH) gene expression. However, mPOU did not affect GH-releasing hormone receptor gene expression. The synergisticd activation mechanism of mPOU and Pit-1 on PRL gene expression is unknown. Next, to clarify whether PRL-or GH-producing cells in human pituitary adenomas have mPOU, serial sections of the specimen were analyzed with anti-hPRL anti-hGH and anti-mPOU antibodies. With anti-mPOU antiserum, PRL- and GH-producing cells yielded a strong signal that was located specifically over the nuclei. On the other hand, no signal was observed when non-functioning pituitary adenoma. Taken together, mPOU appeared to stimulate PRL and GH gene expressions in PRL- and GH- producing pituitary cells, although its pathological significance remained unknown. A targeting vector to knock out mouse Emb (mouse homologue of mPOU) is now being prepared. The Emb knock out mouse may reveal the physiological significance of mPOU.

我们以前从人垂体DNA文库中克隆了一个与PRL基因pit-1结合元件结合的转录因子mPOU。为了阐明mPOU的生理和病理意义，我们首先在瞬时表达和荧光素酶报告基因系统中检测了mPOU对Pit-1调控的基因表达的影响，mPOU和Pit-1协同激活催乳素（PRL）报告基因表达，mPOU和Pit-1相加刺激生长激素（GH）基因表达。然而，mPOU不影响GH释放激素受体基因的表达。mPOU和Pit-1协同激活PRL基因表达的机制尚不清楚。接下来，为了澄清人垂体腺瘤中的PRL或GH产生细胞是否具有mPOU，用抗hPRL、抗hGH和抗mPOU抗体分析标本的连续切片。与抗mPOU抗血清，PRL-和GH-生产细胞产生了强烈的信号，具体位于细胞核。而无功能垂体腺瘤则无信号。两者合计，mPOU似乎刺激PRL和GH基因表达的PRL和GH-生产垂体细胞，但其病理意义仍然未知。目前正在制备敲除小鼠Emb（mPOU的小鼠同源物）的靶向载体。Emb基因敲除小鼠可能揭示了mPOU的生理意义。