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

点击翻译按钮获取中文摘要

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.