Regulation of Aldosterone Synthesis and Secretion
Regulation of Aldosterone Synthesis and Secretion
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DOI：
10.1002/cphy.c130037
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发表时间：
2014-07-01
影响因子：
5.8
通讯作者：
Bollag, Wendy B.
中科院分区：
文献类型：
--
作者：
Bollag, Wendy B.
醛固酮是一种类固醇激素，由肾上腺皮质的外层（肾小球）合成和分泌。醛固酮负责调节钠稳态，从而帮助控制血容量和血压。醛固酮分泌不足可导致低血压和循环休克，特别是在婴儿期。另一方面，过量的醛固酮水平，或那些过高的钠状态，可导致高血压和加剧高血压对多个器官的影响，有助于肾脏疾病，中风，视力丧失和充血性心力衰竭。醛固酮也被认为直接引起终末器官损伤，包括肾脏和心脏。由于醛固酮对心血管系统的生理学和病理生理学的重要性，了解其生物合成和从肾上腺皮质分泌的调节是很重要的。在此，调节醛固酮生产的机制进行了讨论，特别强调参与分泌反应的主要控制器的醛固酮生产，肾素-血管紧张素II系统，血清钾水平和促肾上腺皮质激素的信号通路。所涉及的信号传导途径包括磷脂酶C介导的磷酸肌醇水解、肌醇1，4，5-三磷酸、细胞溶质钙水平、钙内流途径、钙/钙调蛋白依赖性蛋白激酶、二酰基甘油、蛋白激酶C和D、12-羟基二十碳四烯酸、磷脂酶D、促分裂原活化蛋白激酶途径、酪氨酸激酶、腺苷酸环化酶和cAMP依赖性蛋白激酶。对调节醛固酮生物合成的信号事件的完整理解可能允许鉴定用于高血压、原发性醛固酮增多症、充血性心力衰竭、肾脏疾病和其他心血管疾病的治疗干预的新靶点。(C)2014年美国生理学会。
Aldosterone is a steroid hormone synthesized in and secreted from the outer layer of the adrenal cortex, the zona glomerulosa. Aldosterone is responsible for regulating sodium homeostasis, thereby helping to control blood volume and blood pressure. Insufficient aldosterone secretion can lead to hypotension and circulatory shock, particularly in infancy. On the other hand, excessive aldosterone levels, or those too high for sodium status, can cause hypertension and exacerbate the effects of high blood pressure on multiple organs, contributing to renal disease, stroke, visual loss, and congestive heart failure. Aldosterone is also thought to directly induce end-organ damage, including in the kidneys and heart. Because of the significance of aldosterone to the physiology and pathophysiology of the cardiovascular system, it is important to understand the regulation of its biosynthesis and secretion from the adrenal cortex. Herein, the mechanisms regulating aldosterone production in zona glomerulosa cells are discussed, with a particular emphasis on signaling pathways involved in the secretory response to the main controllers of aldosterone production, the renin-angiotensin II system, serum potassium levels and adrenocorticotrophic hormone. The signaling pathways involved include phospholipase C-mediated phosphoinositide hydrolysis, inositol 1,4,5-trisphosphate, cytosolic calcium levels, calcium influx pathways, calcium/calmodulin-dependent protein kinases, diacylglycerol, protein kinases C and D, 12-hydroxyeicostetraenoic acid, phospholipase D, mitogen-activated protein kinase pathways, tyrosine kinases, adenylate cyclase, and cAMP-dependent protein kinase. A complete understanding of the signaling events regulating aldosterone biosynthesis may allow the identification of novel targets for therapeutic interventions in hypertension, primary aldosteronism, congestive heart failure, renal disease, and other cardiovascular disorders. (C) 2014 American Physiological Society.