1992 Fiscal Year Final Research Report Summary
Mechanism for an excessive production of aldosterone in aldosterone producing adenoma
| Project/Area Number |
03670148
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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 |
Pathological medical chemistry
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| Research Institution | School of Medicine Keio University |
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Principal Investigator |
IMAI Michiyo Keio Univ. Sch. of Med. Assistant, 医学部, 助手 (30129340)
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| Co-Investigator(Kenkyū-buntansha) |
MUKAI Kuniaki Keio Univ. Sch. of Med. Assistant, 医学部, 助手 (80229913)
OGISHIMA Tadashi Keio Univ. Sch. of Med. Assistant, 医学部, 助手 (70177153)
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| Project Period (FY) |
1991 – 1992
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| Keywords | aldosterone / aldosterone producing adenome / cytochrome P-450aldo / aldosterone synthase / adrenal cortex / angiotensin II / cytochrome P-450_<ll>beta / corticosteroid |
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| Research Abstract |
In 1989, we successfully purified a cytochrome P-450 which converts deoxycorticosterone efficiently to aldosterone from the zona glomerulosa of rat adrenal cortex(J.Biol. Chcm. 264, 10935). The new cytochrome was distinguishable from cytochrome P-450_<ll>beta responsible for the formation of cortisol or corticosterone from the same substrate. Thus, production of minerallo-and glucocorticoids are catalyzed by different enzymes in rat adrenal cortex, in contrast to the case of bovine adrenal cortex where the hormons are synthesized by a single enzyme cytochrome P-450_<ll>beta. On the basis of such findings, we investigated in this study the mechanism of aldosterone formation in human adrenal cortex with special emphasis on that in aldosterone producing adenoma. The results obtained are summarized as follows.
(1) In human adrenal cortex, there exist two distinct cytochromes P-450, i. e. cytochrome P-450aldo and cytochrome P-450_<ll>beta as in rat adrenocortex.
(2) The cytochrome P-450aldo is exessively expressed in aldosterone producing adenoma.
(3) Using rats as a model, stimulation of aldosterone production by angiotensin II was due to the stimulation of the de novo synthesis of cytochrome P-450aldo through the activation of transcription.
(4) Immunocytochemical studies with specific antibodies proved that cytochrome P-450aldo and cytochrome P-450_<ll>beta are localized exclusively in the zona glomerulosa and fasciculata-reticularis, respectively.
(5) Rat genes which encode cytochrome P-450aldo and cytochrome P-450_<ll>beta, respectively, were isolated and structures of their 5'-flanking regions were charecterized.
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[Publications] Mukai,K., Imai,M., Simada,H., Okada,Y., Ogishima,T., and Ishimura,Y.: "Structural Differences in 5'-Flanking Regions of Rat Cytochrome P-450aldo and P-450_<ll>beta Genes" Biochem. Biophys. Res. Commun. 180. 1187-1193 (1991)
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「研究成果報告書概要(欧文)」より
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[Publications] Ogishima,T., Shibata,H., Shimada,H., Mitani,F., Suzuki,H., Saruta,T., and Ishimura,Y.: "Aldosterone Synthase Cytochrome P-450expressed in the Adrenal with Primary Aldosteronism" J.Biol. Chem. 266. 10731-34 (1991)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Shibata,H., Ogishima,T., Mitani,F., Suzuki,H., Murakami,M., Saruta,T., and Ishimura,Y.: "Regulation of Aldosteron Synthase Cytochrome P-450 in Rat Adrenals by Angiotensin II and Potassium" Endocrinology. 128. 2534-2539 (1991)
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「研究成果報告書概要(欧文)」より
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