Differential effects of down-regulated steroidogenic factor-1 on basal and angiotensin II-induced aldosterone secretion
Differential effects of down-regulated steroidogenic factor-1 on basal and angiotensin II-induced aldosterone secretion
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DOI：
10.3275/7413
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发表时间：
2011-10-01
影响因子：
5.4
通讯作者：
Zhang, X.
中科院分区：
文献类型：
--
作者：
Ouyang, J.;Hu, D.;Zhang, X.
醛固酮合成酶（CYP11B2）负责醛固酮合成的最后一步，并通过多种途径受到血管紧张素-II （Ang II）的重要调控。然而，在病理条件下，如高醛固酮增多症，调节变得紊乱。转录因子甾体生成因子-1 （SF-1）在调节内分泌系统中起重要作用，在醛固酮生成腺瘤（APA）中过度表达，这是醛固酮增多症的常见原因。SF-1的过表达已被广泛研究，但关于抑制SF-1对CYP11B2和Ang II的影响的深入信息很少。在本文中，我们利用SF-1特异性短发卡RNA研究了SF-1下调在基础和Ang ii诱导的CYP11B2表达中的作用。研究发现，抑制性SF-1可降低CYP11B2和醛固酮对Ang II刺激的敏感性，而下调SF-1可增强H295R细胞中CYP11B2的基础表达和醛固酮的产生。考虑到SF-1对醛固酮产生的不同影响，这些结果可能为理解高醛固酮增多症提供新的见解。(j .性。投资管理，34 (3):671-675,2011)
Aldosterone synthase (CYP11B2) is responsible for the final step in aldosterone synthesis and is importantly regulated by angiotensin-II (Ang II) through diverse pathways. However, under pathological conditions, such as in hyperaldosteronism, the regulation becomes disordered. The transcription factor steroidogenic factor-1 (SF-1) is important in regulating the endocrine system and is overexpressed in aldosterone-producing adenoma (APA), a common cause of hyperaldosteronism. Overexpression of SF-1 has been extensively studied, but little in-depth information is available regarding the effects of inhibitory SF-1 on CYP11B2 and Ang II. In this paper, we have investigated the roles of down-regulated SF-1 in basal and Ang II-induced CYP11B2 expression using SF-1-specific short hairpin RNA. Inhibitory SF-1 was found to decrease the sensitivity of CYP11B2 and aldosterone to Ang II stimulation, whereas a down-regulation of SF-1 enhanced basal CYP11B2 expression and aldosterone production in H295R cells. Considering these differential effects of SF-1 on aldosterone production, these results might provide a new insight into the understanding of hyperaldosteronism. (J. Endocrinol. Invest. 34: 671-675, 2011) (C) 2011, Editrice Kurtis