Progesterone potentiates IP3-mediated calcium signaling through Akt/PKB

The activity of cells critically depends on the control of their cytosolic free calcium ion (Ca2+) concentration. The objective of the present study was to identify mechanisms of action underlying the control of the gain of intracellular Ca2+ release by circulating gonadal steroid hormones. Acute stimulation of isolated neurons with progesterone led to IP3 R-mediated Ca2+ transients that depend on the activation of the PI3 kinase/Akt/PKB signaling pathway. These results were confirmed at the molecular level and phosphorylation of IP3 R type 1 by Akt/PKB was identified as the mechanism of action. Hence, it is likely that circulating gonadal steroid hormones control neuronal activity including phosporylation status through receptor- and kinase-mediated signaling. With a direct control of the gain of the Ca2+ second messenger system as a signaling gatekeeper for neuronal activity the present study identifies a novel pathway for interaction of the endocrine and central nervous system. Copyright (c) 2008 S. Karger AG, Basel.