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Endocrine Abstracts (2022) 81 P13 | DOI: 10.1530/endoabs.81.P13

1National Institutes of Health, Bethesda, United States; 2Institut Cochin, Paris, France; 3Institut National de la Santé et de la Recherche Médicale, U1190, European Genomic Institute for Diabetes (EGID), CHU Lille, Lille, France; 4Human Genetics & Precision Medicine, IMBB, FORTH, Heraklion, Greece; 5Research Institute, ELPEN, Pikermi, Athens, Greece

ARMC5 is a tumor suppressor gene responsible for 20 to 40% of Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) with a function that remains unclear. Based on pathway analysis from RNAseq results obtained on zebrafish models of transient Armc5 up- and down-regulation, we identified transcriptional alterations of several members of SIRT1 (sirtuin (silent mating type information regulation 2 homolog) 1) signaling in our models and hypothesized that ARMC5 can regulate SIRT1 and its signaling in adrenocortical cells. Accordingly, the expression of the desacetylase SIRT1 is significantly increased in PBMAH tissues mutated for ARMC5 compared to tumors without mutations. However, this overexpression of SIRT1 is associated with an elevation of the profile of acetylated protein in the absence of ARMC5 suggesting that SIRT1 activity is actually decreased and that SIRT1 expression could increase to maintain its activity. Consistently, the measurement of SIRT activity on PBMAH tissues demonstrate a decrease of its activity when ARMC5is mutated. Similar results are obtained in adrenal cells of 18-month-old Armc5+/- mice that are also hyper-corticosteronemic. Altogether, these data support that ARMC5 could regulate SIRT1 expression and/or activity. In vitro measurement of purified SIRT1 activity in the presence of ARMC5-enriched protein extracts demonstrated that the presence of ARMC5 protein does indeed alter SIRT1 activity. We hypothesize, therefore, that ARMC5 may be a new regulator of SIRT1 function but the underlying mechanism and the consequences of abnormal acetylated proteins on adrenocortical function require further investigation.

Volume 81

European Congress of Endocrinology 2022

Milan, Italy
21 May 2022 - 24 May 2022

European Society of Endocrinology 

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