The mineralocorticoid aldosterone is produced in the adrenal zona glomerulosa (ZG) under the control of the renin–angiotensin II (AngII) system. Primary aldosteronism (PA) results from renin-independent production of aldosterone and is a common cause of hypertension. PA is caused by dysregulated localization of the enzyme aldosterone synthase (Cyp11b2), which is normally restricted to the ZG. Cyp11b2 transcription and aldosterone production are predominantly regulated by AngII activation of the Gq signaling pathway. Here, we report the generation of transgenic mice with Gq-coupled designer receptors exclusively activated by designer drugs (DREADDs) specifically in the adrenal cortex. We show that adrenal-wide ligand activation of Gq DREADD receptors triggered disorganization of adrenal functional zonation, with induction of Cyp11b2 in glucocorticoid-producing zona fasciculata cells. This result was consistent with increased renin-independent aldosterone production and hypertension. All parameters were reversible following termination of DREADD-mediated Gq signaling. These findings demonstrate that Gq signaling is sufficient for adrenocortical aldosterone production and implicate this pathway in the determination of zone-specific steroid production within the adrenal cortex. This transgenic mouse also provides an inducible and reversible model of hyperaldosteronism to investigate PA therapeutics and the mechanisms leading to the damaging effects of aldosterone on the cardiovascular system.

中文翻译：

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肾上腺皮质Gq信号的化学生成激活导致醛固酮增多症并破坏功能区带

盐皮质激素醛固酮是在肾素-血管紧张素II（AngII）系统的控制下在肾上腺肾小球（ZG）中产生的。原发性醛固酮增多症（PA）是由肾素非依赖性醛固酮产生引起的，是高血​​压的常见病因。PA是由醛固酮合酶（Cyp11b2）的定位失调引起的，醛固酮合酶通常限于ZG。Cyp11b2转录和醛固酮的产生主要受AngII激活Gq信号通路的调节。这里，我们报告转基因小鼠的产生与Gq偶联d esigner ř eceptors Ë xclusively一个由ctivated d esigner d地毯（DREADD），特别是在肾上腺皮质。我们显示肾上腺全配体激活Gq DREADD受体触发肾上腺功能区的混乱，在糖皮质激素生产性带状细胞中诱导Cyp11b2。该结果与不依赖肾素的醛固酮产生和高血压一致。DREADD介导的Gq信号终止后，所有参数都是可逆的。这些发现表明，Gq信号足以产生肾上腺皮质醛固酮，并在确定肾上腺皮质区域特异性类固醇产生中暗示了该途径。