Study of Cardiac Steroidogenesis

心脏类固醇生成的研究

• 批准号: 15390249
• 负责人: YOSHIMURA Michihiro
• 金额: $ 9.02万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390249/
• 关键词: aldosterone; dehydroepiandrosterone; ACTH; Heart Failure; Hypertension; ACE; ACE2; Angiotensin II; コルチゾール; CYP17; CYP11B1; CYP11B2; 冠静脈洞

In heart failure or hypertension, it has come to seem that not only circulating aldosterone but also tissue aldosterone has some pathophysiological meanings. In our laboratory, we continuously examined the study of cardiac Steroidogenesis and the relating hormones in humans. In our recently study, we found that aldosterone is secreted from the failing heart ; on the other hand, dehydroepiandrosterone(DHEA) is secreted from the control(healthy) heart in humans(Circulation 2004). In a sense, when the heart is healthy, it has the feature as zona reticularis of the adrenal gland ; however, when the heart condition is deteriorated, it appears the feature of zona glomerulosa. It is interesting to see the switching of the cascades to produce aldosterone or DHEA in relation to the heart conditions ; this is our big challenge of overlapping the concepts of the heart and the adrenal gland.Furthermore, we recently clarified the ACTH secretion from the hearts(ventricles) of patients with hypertens … More ion(J Hypertens 2005). The amount of ACTH secreted from the ventricle was significantly correlated with the grade of blood pressure, suggesting a certain participation of cardiac ACTH to the pathophysiology of essential hypertension. Moreover, there was a positive correlation between cardiac ACTH secretion and cardiac aldosterone secretion, suggesting that, unlike the adrenal gland, ACTH may continue promoting synthesis of aldosterone in the heart. Thus, a new concept called cardiac Hypothalamus-Pituitary-Adrenal(HPA) system study was established in addition to the cardiac RAA system study.Previously, we reported that aldosterone induces the gene expression of angiotensin-converting enzyme(ACE). On the other hand, we found a new action of aldosterone as for the inhibition of the ACE2 gene expression, which was via the mineralocorticoid receptor(MR). Augmentation of the ACE gene expression and inhibition of the ACE2 gene expression by aldosterone would contribute to the deformation of Angiotensin_<1-7> and formation of Angiotensin II, leading to worsening heart failure. Less

在心力衰竭或高血压中，似乎不仅循环醛固酮而且组织醛固酮也具有某些病理生理学意义。在我们的实验室中，我们不断检查心脏类固醇生成和相关激素在人类的研究。在我们最近的研究中，我们发现醛固酮是从衰竭的心脏分泌的;另一方面，脱氢表雄酮（DHEA）是从人类的对照（健康）心脏分泌的（Circulation 2004）。从某种意义上说，当心脏健康时，它具有肾上腺网状结构的特征;而当心脏状况恶化时，它则具有肾小球性结构的特征。有趣的是，看到级联反应的转换产生与心脏状况有关的醛固酮或DHEA;这是我们重叠心脏和肾上腺概念的巨大挑战。此外，我们最近澄清了高血压患者心脏（心室）的ACTH分泌 ...更多信息 离子（J Hypertens 2005）。心室分泌ACTH的量与血压分级显著相关，提示心脏ACTH对原发性高血压的病理生理有一定的参与。此外，心脏ACTH分泌和心脏醛固酮分泌之间呈正相关，这表明，与肾上腺不同，ACTH可能继续促进心脏合成醛固酮。因此，在心脏RAA系统研究的基础上，建立了心脏下丘脑-肾上腺-肾上腺（HPA）系统研究的新概念。另一方面，我们发现了醛固酮抑制ACE 2基因表达的新作用，这是通过盐皮质激素受体（MR）。醛固酮增加ACE基因表达和抑制ACE 2基因表达，可能导致血管紧张素Ⅱ的形成<1-7>和血管紧张素Ⅱ的变形，导致心力衰竭的加重。少

项目成果

Ito T, et al.: "Inhibitory effect of natriuretic peptides on aldosterone synthase gene expression in cultured neonatal rat cardiocytes"Circulation. 107. 807-810 (2003)

Ito T 等人：“利钠肽对培养的新生大鼠心肌细胞中醛固酮合酶基因表达的抑制作用”循环。

Adrenocorticotropic hormone (ACTH) is produced in the ventricle of patients with essential hypertension

原发性高血压患者的心室产生促肾上腺皮质激素（ACTH）

• 发表时间: 2005
• 期刊: J Hypertens 23(2)
• 作者: Mizuno Y;et al.
• 通讯作者: et al.

Plasma levels of B-type natriuretic peptide as a prognostic marker after acute myocardial infarction : a long-time follow-up analysis.

B 型利尿钠肽的血浆水平作为急性心肌梗死后的预后标志物：长期随访分析。

• 发表时间: 2004
• 期刊: Circulation 110(11)
• 作者: Suzuki S;Yoshimura M;Nakayama M;Mizuno Y;Ito T;Nakamura S;Abe K;Yamamoto M;Sakamoto T;Saito Y;Nakao K;Yasue H;Ogawa H.
• 通讯作者: Ogawa H.

Possible association of heart failure status with synthetic balance between aldosterone and dehydroepiandrosterone in human heart

• DOI: 10.1161/01.cir.0000143072.36782.51
• 发表时间: 2004-09-28
• 期刊: CIRCULATION
• 影响因子: 37.8
• 作者: Nakamura, S;Yoshimura, M;Ogawa, H
• 通讯作者: Ogawa, H

Adrenocorticotropic hormone(ACTH) is produced in the ventricle of patients with essential hypertension.

促肾上腺皮质激素（ACTH）是在原发性高血压患者的心室中产生的。

• 发表时间: 2005
• 期刊: J Hypertens 23(2)
• 作者: Mizuno Y;Yasue H;Yoshimura M;Harada E;Fujii H;Nakamura S;Yamamoto N;Ogawa H;Nakao K.
• 通讯作者: Nakao K.