Hwang Ji-yeon, Duncan R Scott, Madry Christian, Singh Meharvan, Koulen Peter
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd., Fort Worth, TX 76107-2699, USA.
Cell Calcium. 2009 Mar;45(3):233-42. doi: 10.1016/j.ceca.2008.10.006. Epub 2008 Dec 9.
Progesterone (P4) is a steroid hormone that plays multiple roles in the central nervous system (CNS) including promoting neuroprotection. However, the precise mechanisms involved in its neuroprotective effects are still unknown. Given that the regulation of the intracellular calcium (Ca(2+)) concentration is critical for cell survival, we determined if inositol 1, 4, 5-trisphosphate receptors (IP(3)Rs) are relevant targets of P4. Using primary hippocampal neurons, we tested the hypothesis that P4 controls the gain of IP3R-mediated intracellular Ca(2+) signaling in neurons and characterized the subcellular distribution and phosphorylation of potential signaling intermediates involved in P4s actions. Our results reveal that P4 treatment altered the intensity and distribution of IP3R immunoreactivity and induced the nuclear translocation of phosphorylated Akt. Further, P4 potentiated IP(3)R-mediated intracellular Ca(2+) responses. These results suggest a potential involvement of P4 in particular and of steroid hormone signaling pathways in general in the control of intracellular Ca(2+) signaling and its related functions.
孕酮（P4）是一种类固醇激素，在中枢神经系统（CNS）中发挥多种作用，包括促进神经保护。然而，其神经保护作用的确切机制仍不清楚。鉴于细胞内钙（Ca(2+)）浓度的调节对细胞存活至关重要，我们确定了肌醇1,4,5-三磷酸受体（IP(3)Rs）是否为P4的相关靶点。我们使用原代海马神经元，测试了P4控制神经元中IP3R介导的细胞内Ca(2+)信号增益的假设，并对参与P4作用的潜在信号中间体的亚细胞分布和磷酸化进行了表征。我们的结果表明，P4处理改变了IP3R免疫反应性的强度和分布，并诱导了磷酸化Akt的核转位。此外，P4增强了IP(3)R介导的细胞内Ca(2+)反应。这些结果表明，P4特别是类固醇激素信号通路可能参与了细胞内Ca(2+)信号及其相关功能的控制。
