Evidence for local aldosterone synthesis in the large intestine of the mouse

H. Launonen, Z. Pang, J. Linden, A. Siltari, R. Korpela, Heikki Vapaatalo

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    Aldosterone, the main physiological mineralocorticoid, regulates sodium and potassium balance in the distal convoluted tubule of the kidney. Aldosterone is synthesized from cholesterol in the adrenal cortex in a sequence of enzymatic steps. Recently however, several tissues or cells e.g. brain, heart, blood vessels, kidneys and adipocytes have been shown to possess capability to produce aldosterone locally, and there is some evidence that this occurs also in the intestine. Colon expresses mineralocorticoid receptors and is capable of synthesizing corticosterone, the second last intermediate on the route to aldosterone from cholesterol. Based on such reports and on our preliminary finding, we hypothesized that aldosterone could be synthesized locally in the intestine and therefore we measured the concentration of aldosterone as well as the protein and gene expression of aldosterone synthase (CYP11B2), an enzyme responsible on aldosterone synthesis, from the distal section of the gastrointestinal tract of 10-week-old Balb/c male mice. It is known that sodium deficiency regulates aldosterone synthesis in adrenal glands, therefore we fed the mice with low (0.01%), normal (0.2%) and high-sodium (1.6%) diets for 14 days. Here we report that, aldosterone was detected in colon and cecum samples. Measurable amounts of CYP11B2 protein were detected by Western blot and Elisa analysis from both intestinal tissues. We detected CYP11B2 gene expression from the large intestine along with immunohistochemical findings of CYP11B2 in colonic wall. Sodium depletion increased the aldosterone concentration in plasma compared to control and high-sodium groups as well as in the intestine compared to mice fed with the high-sodium diet. To summarize, this study further supports the presence of aldosterone and the enzyme needed to produce this mineralocorticoid in the murine large intestine.

    Original languageEnglish
    Pages (from-to)807-815
    Number of pages9
    JournalJOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
    Volume72
    Issue number5
    DOIs
    Publication statusPublished - Oct 2021
    Publication typeA1 Journal article-refereed

    Keywords

    • Aldosterone
    • Aldosterone synthase
    • CYP11B2
    • Extra-adrenal aldosterone synthesis
    • Gene and protein expression
    • Intestine
    • Local mineralocorticoid production
    • Sodium deficiency

    Publication forum classification

    • Publication forum level 1

    ASJC Scopus subject areas

    • Physiology
    • Pharmacology

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