Abstract:
Aldosterone is a steroid hormone that is important for maintaining the volume and ionic composition of extracellular fluids and is produced in the zona glomerulosa of the adrenal cortex. The basic mechanisms controlling aldosterone secretion are known. However, more detailed studies on the regulation of aldosterone secretion often fail due to the lack of suitable models: although secretion can be studied in cultured adrenocortical cells under defined conditions, the differentiation status of the cells is difficult to control and the complex anatomy of the adrenal cortex is lost. In living animals, the physiological context is intact, but the influences are manifold and the examination conditions cannot be sufficiently controlled. One method that closes the gap between cell models and studies in living animals is the isolated perfused adrenal gland. In the past, this method has provided important data on the pathophysiology of adrenal glands from larger animals, but the technique was not used in mice. Here, we developed a method for isolation and perfusion of the mouse adrenal gland to study aldosterone secretion. This technique preserves the complex anatomical and functional context of the mouse adrenal cortex, to ensure defined experimental conditions and to minimize extra-adrenal influences. Initial series of experiments with the ex vivo perfused mouse adrenal gland show that this model offers the possibility for unique insights into pathophysiological regulatory principles and is suitable for the use of genetically modified mouse models.
摘要:
醛固酮是一种类固醇激素,对于维持细胞外液的体积和离子组成很重要,并且在肾上腺皮质的肾小球带中产生。控制醛固酮分泌的基本机制是已知的。然而,由于缺乏合适的模型,对醛固酮分泌调节的更详细研究通常会失败:尽管可以在确定的条件下在培养的肾上腺皮质细胞中研究分泌,细胞的分化状态难以控制,肾上腺皮质的复杂解剖结构丢失。在活着的动物中,生理环境是完整的,但是影响是多方面的,并且无法充分控制检查条件。在活体动物中缩小细胞模型和研究之间差距的一种方法是分离的灌注肾上腺。在过去,这种方法为大型动物的肾上腺病理生理学提供了重要数据,但该技术并未用于小鼠。这里,我们开发了一种分离和灌注小鼠肾上腺以研究醛固酮分泌的方法。该技术保留了小鼠肾上腺皮质的复杂解剖和功能环境,以确保确定的实验条件,并尽量减少肾上腺外的影响。体外灌注小鼠肾上腺的初始系列实验表明,该模型提供了对病理生理调节原理的独特见解的可能性,并且适用于转基因小鼠模型的使用。