2003 Fiscal Year Final Research Report Summary
Molecular analysis of steroidogenesis in the field of obstetrics and gynecology
| Project/Area Number |
12470338
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
SUGAWARA Teruo Hokkaido Univ., Grad.School of Med., Inst., 大学院・医学研究科, 助手 (40250451)
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| Co-Investigator(Kenkyū-buntansha) |
HOSHI Nobuhiko Kitasato University School of Verternity Medicine and Animal Sciences, 獣医学部, 助教授 (10209223)
FUJIEDA Kenji Asahikawa Medical College, School of Med., Prof., 医学部, 教授 (60173407)
SAKURAGI Noriaki Hokkaido Univ., Grad.School of Med., Prof., 大学院・医学研究科, 教授 (70153963)
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| Project Period (FY) |
2000 – 2003
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| Keywords | StAr / SF-1 / DAX-1 / Ovary / RIP140 / Endometrial Cancer / StAR protein binding protein / steroid hormone |
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| Research Abstract |
Steroidogenic acute regulatory (StAR) protein plays a critical role in the movement of cholesterol from the outer to the inner mitochondrial membrane. We found that the co-regulator RIP 140 interacts with SF-1 in the yeast two-hybrid system. The inhibitory effect of RIP 140 on human StAR promoter activity was dependent upon the presence of SF-1. We also examined the effect of induction of cAMP with transfection with AhR or ARNT. AhR plays a role in the promoter activity of the human StAR gene and that the effect of AhR on StAR gene expression may cause a disturbance to the human endocrine system.
Endometrial carcinoma is a common malignancy of the genital tract. We examined the expressions of human steroidogenic acute regulatory (StAR) protein, P450 side-chain cleavage enzyme (P450scc), 17α-hydroxylase/17, 20-desmolase (P45017α) and aromatase (P450arom) in endometrial carcinoma cells to clarify the ability of these cells to produce steroid hormones. Endometrial carcinoma cells express enzymes that are associated with production of steroid hormones. Locally produced steroid hormones may have effects on tumor proliferation and tumorigenesis.
A StAR mutant protein lacking the first 62 amino acids (N-62 StAR protein) has been reported to be as effective as wild-type StAR protein. We examined the mechanism by which StAR protein stimulates steroidogenesis. The clone translated product was named StAR-binding protein (SBP). The amount of steroid hormones produced by steroidogenic cells subjected to siRNA treatment was less then that produced by control cells. SBP binds StAR protein in cells and enhances the ability of StAR protein to promote syntheses of steroid hormones.
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