Signaling Interactions in the Adrenal Cortex
Signaling Interactions in the Adrenal Cortex
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肾上腺皮质中的信号相互作用
作者：
A. Spät;L. Hunyady;G. Szanda
醛固酮分泌的主要生理刺激是血管紧张素II（AII）和细胞外K+，而皮质醇的产生主要受束状细胞中促肾上腺皮质激素（ACTH）的调节。AII触发Ca 2+从内部存储器释放，随后是存储器操作和电压依赖性Ca 2+进入，而K+诱发的去极化激活电压依赖性Ca 2+通道。ACTH主要通过cAMP的形成和随后通过蛋白激酶A的蛋白磷酸化起作用。Ca ~（2+）和cAMP均能促进胆固醇向线粒体内膜的转运。胞质Ca 2+信号被转移到线粒体基质中并增强吡啶核苷酸还原。NADH的形成增加导致ATP产生增加，而NADPH的形成支持类固醇产生。实际上，肾上腺皮质功能的控制要复杂得多，第二信使相互交叉，相互修改彼此的通路。胞浆Ca ~（2+）和cGMP均能调节cAMP代谢，而cAMP可增强Ca ~（2+）释放和电压激活的Ca ~（2+）通道活性。此外，线粒体Ca 2+信号导致细胞器内cAMP的形成，这进一步增强了醛固酮的产生。维持的醛固酮和皮质醇分泌通过Ca 2+和cAMP的同时作用而优化，如在对AII的响应期间Ca 2+内流（诱导cAMP形成）和Ca 2+释放的明显协同作用所例示。因此，平行信号转导通路的交叉作用不仅仅是细胞内的好奇心，而是实质性的现象，它微调生物反应。我们的审查集中在这些功能相关的相互作用之间的Ca 2+和环核苷酸信号转导途径迄今为止描述的肾上腺皮质。
The major physiological stimuli of aldosterone secretion are angiotensin II (AII) and extracellular K+, whereas cortisol production is primarily regulated by corticotropin (ACTH) in fasciculata cells. AII triggers Ca2+ release from internal stores that is followed by store-operated and voltage-dependent Ca2+ entry, whereas K+-evoked depolarization activates voltage-dependent Ca2+ channels. ACTH acts primarily through the formation of cAMP and subsequent protein phosphorylation by protein kinase A. Both Ca2+ and cAMP facilitate the transfer of cholesterol to mitochondrial inner membrane. The cytosolic Ca2+ signal is transferred into the mitochondrial matrix and enhances pyridine nucleotide reduction. Increased formation of NADH results in increased ATP production, whereas that of NADPH supports steroid production. In reality, the control of adrenocortical function is a lot more sophisticated with second messengers crosstalking and mutually modifying each other’s pathways. Cytosolic Ca2+ and cGMP are both capable of modifying cAMP metabolism, while cAMP may enhance Ca2+ release and voltage-activated Ca2+ channel activity. Besides, mitochondrial Ca2+ signal brings about cAMP formation within the organelle and this further enhances aldosterone production. Maintained aldosterone and cortisol secretion are optimized by the concurrent actions of Ca2+ and cAMP, as exemplified by the apparent synergism of Ca2+ influx (inducing cAMP formation) and Ca2+ release during response to AII. Thus, cross-actions of parallel signal transducing pathways are not mere intracellular curiosities but rather substantial phenomena, which fine-tune the biological response. Our review focuses on these functionally relevant interactions between the Ca2+ and the cyclic nucleotide signal transducing pathways hitherto described in the adrenal cortex.
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影响因子：
--
作者：
Bassett, MH;Suzuki, T;Rainey, WE
通讯作者：
Rainey, WE
血管平滑肌 I 型血管紧张素 II 受体 mRNA 因环 AMP 升高剂而不稳定。
影响因子：
3.6
作者：
Wang,X;Nickenig,G;Murphy,TJ
通讯作者：
Murphy,TJ
影响因子：
3.5
作者：
Xing Y;Parker CR;Edwards M;Rainey WE
通讯作者：
Rainey WE
血管紧张素-II 通过 1 型受体发挥作用，抑制绵羊肾上腺皮质细胞中 17 α-羟化酶细胞色素 P450 的表达。
影响因子：
4.8
作者：
Bird,IM;Magness,RR;Mason,JI;Rainey,WE
通讯作者：
Rainey,WE
通过表达蛋白激酶抑制剂/增强型绿色荧光融合蛋白来抑制环 AMP 依赖性激酶，可减弱血管平滑肌细胞中血管紧张素 II 诱导的 1 型 AT1 受体 mRNA 下调。
影响因子：
3.6
作者：
Wang,X;Murphy,TJ
通讯作者：
Murphy,TJ