Faculty of Medicine, Pharmacology, University of Helsinki, Helsinki, Finland.
Faculty of Medicine, Human Microbiome Research Program, University of Helsinki, Helsinki, Finland.
J Physiol Pharmacol. 2022 Aug;73(4). doi: 10.26402/jpp.2022.4.03. Epub 2023 Jan 20.
Aldosterone is the most important mineralocorticoid hormone regulating water and electrolyte absorption in the distal convoluted tubule of the kidney. Recently, we detected the presence of the whole chain of aldosterone production from the precursor corticosterone, transcription factor liver receptor homologue-1 (LRH-1), the aldosterone synthase enzyme protein (CYP11B2) as well as the gene to the final product aldosterone in murine large intestine. Here, we decided to correlate the amount of this synthase protein with its enzymatic activity in different parts of gastrointestinal tract and also with the aldosterone concentration in the respective tissue. Considering the physiological behavior of the animals in light and dark environment, we measured these variables at four time points - two in the light, the others during darkness. In vitro activity of CYP11B2 was measured as the amount of aldosterone formed from the precursor deoxycorticosterone using enzyme preparations from homogenized intestinal sections. CYP11B2 enzyme activity was higher in the large than in the small intestine. In ileum and colon, the CYP11B2 activity increased in the dark time. The highest aldosterone concentration was detected in the dark in the large intestine. In summary, enzyme activity of CYP11B2 was present in all parts of intestine; the large intestine formed more aldosterone during the darkness. No difference was seen in any of the variables between the early and late light hours.
醛固酮是调节肾脏远曲小管水和电解质吸收的最重要的盐皮质激素。最近,我们在小鼠大肠中检测到了醛固酮产生的整个链条,包括前体皮质酮、转录因子肝受体同系物-1(LRH-1)、醛固酮合酶蛋白(CYP11B2)以及最终产物醛固酮。在这里,我们决定将这种合成酶蛋白的数量与其在胃肠道不同部位的酶活性以及相应组织中的醛固酮浓度相关联。考虑到动物在光照和黑暗环境中的生理行为,我们在四个时间点测量了这些变量-两个在光照下,另外两个在黑暗中。使用来自匀浆肠段的酶制剂,通过从前体脱氧皮质酮形成的醛固酮量来测量 CYP11B2 的体外活性。CYP11B2 酶活性在大肠中高于小肠。在回肠和结肠中,CYP11B2 活性在黑暗时间增加。在大肠中,在黑暗中检测到的醛固酮浓度最高。总之,CYP11B2 酶活性存在于肠道的所有部位;在黑暗中,大肠形成了更多的醛固酮。在任何变量中,光照早期和晚期之间均无差异。