| Project/Area Number |
12836001
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
MORI Tsukasa Hokkaido Univ., Grad. School of Fish., Inst., 大学院・水産科学研究科, 助手 (60241379)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Estrogen receptor / rainbow trout / molecular dynamics / 環境ホルモン |
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| Research Abstract |
In primary cultures of immature male rainbow trout (rt) hepatocytes, vitellogenin (Vg) gene expression regulated by E2 via the estrogen receptor (ER). However, steroids other than estrogens can also stimulate Vg gene expression. These steroids are hardly converted into E2 during incubation and their stimulatory activity is completely inhibited by tamoxifen implying rtER involvement. These steroids have no or a slightly positive charge on the Connolly surface. In contrast, steroids that failed to stimulate Vg gene expression had a strong positive or negative charge around rings C and D due to polarization. The ammo acid sequences of the ligand binding domains (LBD) of rtER and human ERa have 57.7% homology; only one amino acid differs in the presumed steroid binding site. We modeled the three-dimensional structure of the LBD of rtER using X-ray crystallographic data for hERa in order to investigate the fit (structural and electrostatic) between steroid and rtER. Two factors are essential for binding to rtER: (i) hydroxyl or carbonyl groupsi near C3 andI C17 of the steroids (hydrophilic regions) that can form hydrogen bonds with His(489), Arg(359) and Glu(318), (ii) a hydrophobic steroid nucleus that interacts with a hydrophobic region of the rtER LBD through van der Waals forces. If polar functional groups are present, the hydrophobic interaction between steroid and the rtER LBD is considerably weakened.
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