Progesterone potentiates IP(3)-mediated calcium signaling through Akt/PKB.
The activity of cells critically depends on the control of their cytosolic free calcium ion (Ca(2+)) concentration. The objective of the present study was to identify mechanisms of action underlying the control of the gain of intracellular Ca(2+) release by circulating gonadal steroid hormones. Acute stimulation of isolated neurons with progesterone led to IP(3)R-mediated Ca(2+) 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 IP(3)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 Ca(2+) 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.
Koulen
Peter
P
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107-2699, USA. pkoulen@hsc.unt.edu
Madry
Christian
C
Duncan
R Scott
RS
Hwang
Ji-Yeon
JY
Nixon
Everett
E
McClung
Nathalie
N
Gregg
Elaine V
EV
Singh
Meharvan
M
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000737:chemistry; D015640:Ion Channel Gating / Q000187:drug effects; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D051245:Retinal Bipolar Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
D053496:Inositol 1,4,5-Trisphosphate Receptors; D011980:Receptors, Progesterone; D011374:Progesterone; D015544:Inositol 1,4,5-Trisphosphate; D051057:Proto-Oncogene Proteins c-akt