1994 Fiscal Year Final Research Report Summary
Cloning of homeobox genes involved in the differentiation of placental cells producing peptide hormones
| Project/Area Number |
04454559
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Nagoya University |
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Principal Investigator |
SEO Hisao Nagoya Univ., Res.Inst.Environ. Med.Professor, 環境医学研究所, 教授 (40135380)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAMOTO Norihiro Nagoya Univ., Res.Inst.Environ. Med.Research Associate, 環境医学研究所, 助手 (10221615)
MURATA Yoshiharu Nagoya Univ., Res.Inst.Environ. Med.Associate Professor, 環境医学研究所, 助教授 (80174308)
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| Project Period (FY) |
1992 – 1994
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| Keywords | Pax-8 / placenta / thyroglobulin / redox |
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| Research Abstract |
Placental villi synthesize hormones such as plaental lactogen (PL) and chorionic gonadotropin (CG). These peptide hormones play important role for the maintenace of pregnacy and the development and growth of fetus. It is well known that the genes for placental lactogen and pituitary grwoth hormone (GH) share sequence homology and originate from a common ancestral gene. Also chorionic gonadotropin and pituitary gonadotropins (luteinizing hormone=LH and follicle stimulating hormone=FSH) and thyroid stimulating hormone (TSH) originate from a common ancestral gene. Recently, it has been shown that tissue specific expression of GH and TSH is controlled by a transcriptional factor, Pit-1, belonging to POU family protein. This finding lead us to postulate that POU family transcription factor (s) may play important role for the expression of placental hormones. It was thsu investigated whether placental tissue expresses transcription factor belonging to POU family. To study whether Pit-1 is ex
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pressed in human placental tissue or not, a cDNA coding for human Pit-1 was cloned by reverse transcription-polymerase chain reaction (RT-PCR) using pituitary RNA as a template. Using this cDNA,it was revealed that placental tissue does not express Pit-1 gene, suggesting other transcription factor is involved in the placental tissue expression of PL and CG.The search for the expression of POU family by RT-PCR revealed that Oct-1 is expressed in placenta. The result indicated that Pit-1 like transcription factor might be present in placenta since Oct-1 heterodimerizes with Pit-1 and augments its action.
Search for other transciption factors revealed that Pax-8, belonging to paired domain protein is also expressed in the placenta. We have demonstrated that Pax-8 play important role for the thyroid specific expression of thyroglobulin gene. The results indicate the possible involvement of Pax-8 for the placental specific expression of peptide hormones. Recently it was demonstrated that post-translational modification such as phosphorylation and reduction is required for the activation of transcription factors. For example, Pit-1 is activated by phosphorylation. However, it has never been studied whether post-translational midification is also required for the activation of Pax-8. Our study revealed that Pax-8 is activated by reduction but not by phosphorylation. It is thus speculated that redox regulation is important for the tissue specific expression of placental genes. Less
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