Abstract

Cell-cycle dysregulation and increased steroid production are frequent effects of adrenocortical malignancies.The control of the cell cycle and steroid production are both impacted by cAMP/PKA signalling. We looked into the regulation of steroidogenesis and the role of PKA in adrenocortical cells using cell synchronisation in the various cell-cycle phases. At G2 phase, cells had their highest levels of PKA activity, while at G1 phase, they had their lowest levels. In all synchronised groups, PRKACA overexpression or cAMP stimulation increased PKA activity and promoted steroidogenesis, but these effects alone are insufficient to promote cell-cycle advancement. Only in cells in G1, PRKAR1A inactivation increased PKA activity, promoted STAR gene expression, and prompted cell-cycle advancement in all groups. These results demonstrate a close connection between steroidogenesis and the cell cycle in ACTs. Moreover, PRKAR1A plays a critical role in controlling how PKA activity affects adrenocortical cells' ability to advance through the cell cycle and steroidogenesis.