ETO Yoshikatsu Jikei University School of Medicine, Professor, 医学部, 教授 (50056909)
YOSHIKAWA Hideki Jikei University School of Medicine, Assistant, 医学部, 助手 (60328367)
NOZAKI Kazuyuki Jikei University School of Medicine, Assistant, 医学部, 助手 (80312023)
|Budget Amount *help
¥3,400,000 (Direct Cost : ¥3,400,000)
Fiscal Year 2004 : ¥1,600,000 (Direct Cost : ¥1,600,000)
Fiscal Year 2003 : ¥1,800,000 (Direct Cost : ¥1,800,000)
The aim of our research is to elucidate the mechanism of the development and differentiation of the human pituitary gland. In this study, we analyzed candidate genes for two male sibling cases of familial congenital panhypopituitarism with central diabetes insipidus. These cases are thought to be a good model to research the human pituitary development and differentiation, since they have severe deficiency of all pituitary anterior hormones and their brain MRIs reveal severe pituitary hypoplasia. At the first year, genetic analysis of pituitary transcription factors (LHX3,LHX4,PTX1,PTX2,HESX1, and BRN2) was performed for our cases using PCR-SSCP and DNA sequencing methods. However, no mutations in these genes have been identified. Next year, we aimed at Trf1,BMP4, and EGF8, which are involved in the development of the diencephalons. derived from neural ectoderm. No abnormalities have been found, although we carried out molecular analysis of Trf1,BMP4, and EGF8 genes. In addition, we also performed the mutational analysis of the transcription factor SOX3 gene, which is essential for the formation of the hypothalamo-pituitary axis, but no mutations were detected in this gene. Based on these findings, it is speculated that the cause of familial congenital panhypopituitarism such as our cases would be due to abnormality of an unknown gene which is involved in the pituitary development and differentiation during early stage. As the next strategy, we started physical mapping for a new candidate gene. We focused on the X chromosome because Solomon et al. recently showed increased gene levels at Xq26-27 associated with X-linked hypopituitarism. We are now trying linkage analysis using microsatellite markers which are located in the X chromosome. At present, no candidate regions, which give a good lod score, have been detected yet. Linkage analysis is under way.