| Project/Area Number |
07044277
|
|---|
| Research Category |
Grant-in-Aid for international Scientific Research
|
| Allocation Type | Single-year Grants |
|---|
| Section | Joint Research |
|---|
| Research Field |
内分泌・代謝学
|
|---|
| Research Institution | KYUSHU UNIVERSITY |
|---|
Principal Investigator |
NAWATA Hajime Kyushu University, Faculty of Medicine, Professor, 医学部, 教授 (10038820)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MOROHASHI Kenishirou Okazaki National Research Institutes, National Institute for Basic Biology, Prof, 基礎生物学研究所, 教授 (30183114)
IKUYAMA Showichiro Kyushu University, Faculty of Medicine, Research Associate, 医学部, 助手 (20184393)
YANASE Toshihiko Kyushu University, Faculty of Medicine, Research Associate, 助手 (30239818)
TAKAYANAGI Ryoichi Kyushu University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (30154917)
WATERMAN Mic バンダービルト大学, 医学部, 教授
WATERMAN Michael R Vanderbilt University, School of Medicine, Biochemistry, Chairman
香川 憲夫 バンタービルト大学, 医学部, 助教授
|
|---|
| Project Period (FY) |
1995 – 1997
|
| Project Status |
Completed (Fiscal Year 1997)
|
| Budget Amount *help |
¥8,400,000 (Direct Cost: ¥8,400,000)
Fiscal Year 1997: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1995: ¥2,900,000 (Direct Cost: ¥2,900,000)
|
|---|
| Keywords | steroid hormone / transcription factor / P450 / steroidogenic factor 1 / DAX-1 / Ad4BP / congenital adrenal hypoplasia / sex differentiation |
|---|
| Research Abstract |
1. Analyzes of the transcription factors for steroidogenic P450 genes. (1) Cloning of human Ad4BP (SF-1) gene and cDNAs for CRS1-BP and E box binding protein. The size of human Ad4BP gene was about 30kb containing 7 exons, encoding 461 amino acids. E box, which was shown to be essential for transcription of Ad4BP gene, was present in the promoter region of human Ad4BP gene. CRS1-BP,a factor for cAMP responsiveness of CYP17 gene, was shown to be PbX-1. A cDNA for E box binding protein was isolated from neonatal rat testis. (2) Effects of Ad4BP and DAX-1 on the transcription of P450 gens. Ad4BP enhanced the transcription of P450SCC,P45011beta and P45017alpha genes, but DAX-1 suppressed. Ad4BP and DAX-1 thus interact each other.
2. Analyzes of Ad4BP and DAX-1 genes in congenital adrenal hypoplasia (CAH). Six males with CAH had the mutations in their DAX-1 genes : one was missense mutation and the other five were nonsense mutations due to stop codon or frame shift, and in one family, the parents of one male patient had no mutations in DAX-1 gene, indicating that CAH due to DAX-1 mutation can originate from a germ linen mutation. Three females with CAH,however, had mutation neither in Ad4BP nor DAX-1 gene, suggesting that unidentified factor (s) other than Ad4BP or DAX-1 still exists as the cause of CAH.
|
