1995 Fiscal Year Final Research Report Summary
Molecular Genetic Studies on the Biosyntesis of Steroid Hormones
| Project/Area Number |
06454169
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Kochi Medical School |
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Principal Investigator |
SHIZUTA Yutaka Kochi Medical School Professor, 医学部, 教授 (50025631)
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| Co-Investigator(Kenkyū-buntansha) |
NOMOTO Satoshi Kochi Medical School Instructor, 医学部, 助手 (70271096)
MIYAHARA Kaoru Kochi Medical School Instructor, 医学部, 助手 (30229877)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Steroid Hormones / Aldosterone / Cortisol / Biosynthesis / Congenital diseases / Estrogen / Transcriptional Factor / NF-IL6 |
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| Research Abstract |
Aldosterone is the major mineralocorticoid in the adrenal cortex. We have cloned steroid 18-hydroxylase (P-450_<C18>) and demonstrated that this enzyme catalyzes the penultimate and ultimate steps in the synthesis of aldosterone, which had been considered to be catalyzed by corticosterone methyl oxidase (CMO) type I and type II.This observation indicates that CMO I and CMO II deficiencies are derived from two different mutations in the P-450_<C18> gene. Sequence analysis of this gene of CMO I deficient patients has revealed that the gene is completely inactivated by a frameshift to form a stop codon due to a 5bp nucleotide deletion in exon 1. Further analysis of CMO II deficient patients has revealed two point mutations in exon 3 and exon 7. These results provide molecular genetic evidence to show that both diseases are caused by mutations in the single gene encoding p-450_<C18>.
In the next experiment we have elucidated the locus of a defect of P-450_<11beta> gene in 11beta-deficient patients who are not able to produce cortisol.
Finally, we have demonstrated the intrinsic importance of NF-IL6 in the transcriptional regulation of the estrogen synthase gene expression.
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