1994 Fiscal Year Final Research Report Summary
Molecular mechanism of aldosterone biosynthesis
| Project/Area Number |
05680553
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional biochemistry
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
TAKEMORI Shigeki Hiroshima Univ., Faculty of Int.Arts & Sciences, Professor, 総合科学部, 教授 (60019461)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAZAKI Takeshi Hiroshima Univ.Faculty of Int.Arts & Sciences, Research associates, 総合科学部, 助手 (30192397)
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| Project Period (FY) |
1993 – 1994
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| Keywords | P-450 (11beta) / Steroidogenesis / Adrenal cortex / P-450 (scc) / Aldosterone / Steroid hormone |
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| Research Abstract |
In adrenal cortex, a mineralocorticoid, aldosterone, is produced in the zona glomerulasa (ZG), but not in the zonae fasciculata-reticularis (ZFR). Bovine adrenal P-450 (11beta) catalyzes the terminal steps in both aldosterone and corticosterone synthesis from deoxycorticosterone (DOC). Since bovine adrenal P-450 (11beta) is distributed throughout the three zones, the zone-specific aldosterone synthesis would not be due to difference in P-450 species in the mitochondria of each zone as demonstrated in adrenals of mouse, rat and human. Therefore, aldosterone-synthesizing activity inherent to P-450 (11beta) in ZFR must be suppressed by certain factor. Using the P-450 proteoliposomes, we noted that the suppression of the aldosterone synthesizing activity might be due to interaction between P-450 (11beta) and P-450 (scc). The difference of interactions between the two P-450 proteins in each inner mitochondrial membranes from ZG and ZFR was demonstrated using immuno-inhibition and crosslinking experiments, suggesting that P-450 (scc) modulates the activity of P-450 (11beta) within mitochondrial membranes. The reactions of corticosterone and aldosterone synthesis from DOC were studied kinetically using P-450 (11beta) -proteoliposomes and Tween 20-solubilized P-450 (11beta). The catalytic properties of the latter were virtually the same as those of proteoliposomes containing P-450 (11beta) and P-450 (scc). In the reactions of P-450 (11beta) complexed with P-450 (scc) in proteoliposomes and Tween 20-solubilized P-450 (11beta). corticosterone as an intermediate easily leaves from the catalytic site of P-450 (11beta). consequently hindering three successive monooxygenation reactions for DOC to form aldosterone as the final product.
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