Involvement of ARMC5 in proliferation and cell cycle control of human cell cultures from adrenal nodules of primary macronodular adrenocortical hyperplasia (PMAH)

Update of Genetic and Molecular Causes of Adrenocortical Hyperplasias Causing Cushing Syndrome

“…One main difference between the mouse models invalidated for Armc5 and PBMAH is then, this absence of nodular structure 72 73 that can be explained by species difference as well and/or an additional molecular alteration still unknown in PBMAH that would be responsible for the macronodules development. However, as it has been demonstrated in human adrenocortical cells, ARMC5 has both a pro-apoptotic function and an ability to control negatively the cell proliferation 57 71 , the macronodules observed in PBMAH patients can then, be caused by the association of a decrease in cell death and an increase of cell proliferation overtime.…”

“…Although ARMC5 function remains unclear, in vitro studies first suggest that ARMC5 controls adrenocortical steroidogenesis. Indeed, ARMC5 knockdown either in the human adrenocortical carcinoma cells line H295R or in cell culture from PBMAH wild-type for ARMC5 leads to a down-regulation of steroidogenic enzymes expression 57 71 . Consistently, mouse model heterozygote for Armc5 ( Armc5 +/– ), that are therefore, genetically close to PBMAH patients develop a decrease in glucocorticoids at 12 months supporting Armc5 role in steroidogenesis regulation 72 .…”