| Project/Area Number |
60480273
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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 |
内分泌・代謝学
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| Research Institution | Kyushu University |
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Principal Investigator |
NAWATA Haiime (1987) Professor, Kyusyu University Faculty of Medicine,, 医学部, 教授 (10038820)
井林 博 (1985-1986) 九大, 医学部, 教授 (50010137)
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| Co-Investigator(Kenkyū-buntansha) |
YANASE Toshihiko Research fellow, Medicine, Kyusyu University Faculty of, 医学部, 医員
HAJI Masafumi Research associate, Medicine, Kyusyu University Faculty of, 医学部, 助手 (10136468)
OHASHI Masao Research associate, Medicine, Kyusyu University Faculty of, 医学部, 助手 (90117078)
IBAYASHI Hiroshi Professor emeritus, Kyusyu University, 名誉教授 (50010137)
樋口 和巳 九州大学, 医学部, 医員
名和田 新 九州大学, 医学部, 講師 (10038820)
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| Project Period (FY) |
1985 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1987: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1985: ¥3,600,000 (Direct Cost: ¥3,600,000)
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| Keywords | Adrenorphin / Leumorphine / Prolactin / Preproenkephalin A and B / Preproenkephalin A mRNA / hANP / Epinephrine / Opioid peptide / Catecholamine / 心房性Na利尿ペプチド(α-hANP) / 加合と副腎 / Glucocortieoicd受容体 |
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| Research Abstract |
We examined the effects of human atrial natriuretic peptide(hANP), preproenkephalin A and B derived opioid peptides, prolactin and glucocorticoid hormone as modulators on the synthesis and secretions of adrenocortical and medullary hormones. We demonstrated hANP receptor on the human and bovine adrenocortical cell membranes. hANP loading tests in healthy human subjects and the addition of hANP on cultured human adrenocortical cells in vitro revealed the direct suppressive effects on the secretion of not only aldosterone, but also cortisol, DHEA, DHEA-S, androstenedione and 19-OH-andro stenedione, suggesting that hANP blocks the adrenocortical steroidogenic pathway in front of the cholesterol desmolase reaction. On the other hand no suppression of serum aldosterone and cortisol in vivo and in vitro was observed in the patients with primary aldosteronism and Cushing's syndrome by hANP. The defect of hANP receptor was demonstrated on the membranes of functional adrenocortical adenoma cell
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s. In women with hyperprolactinemia there was significant correlation between serum prolactin and DHEA sulfate and DHEA. Prolactin in combination with ACTH potentiated the effect of ACTH on DHEA-S and DHEA, but not on androstenedione and cortisol in cultured human and bovine adrenocortical cells, suggesting that synergistic effect of prolactin on adrenal androgen secretion may result from partial inhibition of adrenal 3B-hydroxysteroid dehydrogenase. Dexamethasone(Dex) caused the increase in ornithine decarboxylase activity and suppressed the increase in cortisol production by ACTH. Auto regulation of cortisol production in adrenal cortex by glucocorticoid was demonstrated. We demonstrated the presence of not only catecholamine, but also met-enkephalin, met-enkephalin-AGL, leu-enkephalin, adrenorphin, neoendorphin and dynorphin and calcitonin, somatostatin, CRF, ACTH, VIP, GRF, ANP and 7B2 in bovine adrenal medulla and pheochromocytoma (Ph.). Glucocorticoid receptor was demonstrated in the cytosol of bovine adrenal medulla and pheochromocytoma. Dexamethasone increases both catecholamine contents and preproenkephalin A and B-derived opioid peptide contents and preproenkephalin A mRNA in the cultured bovine adrenomedullary cells and pheochromocytoma slls. Dexamethasone and micotine have a synergistic effect on the induction of preproenkephalin A mRNA. Secreted opioid peptides derived from preproenkephalin A and B inhibit the secretion of catecholamines. Autoregulabtion of catecholamine synthesis and secretion by opioid peptides was demonstrated. Larger amounts of met-enkephalin were found in medullary Ph. than extramedullary ones. Extramedullary Ph. showed a sustained hypertension, whereas medullary Ph. showed paroxysmal hypertension. The differences in the tissue content of opioid peptides may play an important role in hypertension. Less
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