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

我们先前从人脑垂体DNA文库中克隆了一个转录因子mPOU，它与PRL基因的Pit-1结合DNA元件结合。为了阐明生理和病理意义，我们首先研究了mPOU在瞬时表达和荧光素酶报告基因系统中对Pit-1调控基因表达的影响，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。但mPOU不影响GH释放激素受体基因的表达。MPOU和Pit-1对PRL基因表达的协同激活机制尚不清楚。接下来，为了弄清人垂体腺瘤中的PRL或GH产生细胞是否存在mPOU，用抗hPRL、抗hGH和抗mPOU抗体对标本进行了连续切片分析。在抗mPOU抗血清的作用下，PRL和GH产生的细胞产生了强烈的信号，该信号特异性地位于细胞核上方。另一方面，当无功能的垂体腺瘤时，观察不到任何信号。综上所述，mPOU似乎能刺激产生PRL和GH的垂体细胞中PRL和GH基因的表达，尽管其病理意义尚不清楚。一种敲除小鼠emb(mPOU的小鼠同源基因)的靶向载体正在制备中。Emb基因敲除小鼠可能揭示了mPOU的生理意义。

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.