17-Beta-estradiol-mediated activation of extracellular-signal regulated kinase, phosphatidylinositol 3-kinase/protein kinase B-Akt and N-methyl-D-aspartate receptor phosphorylation in cortical synaptoneurosomes.
In addition to its well-known activational mechanism, the steroid hormone 17-beta-estradiol (E2) has been shown to rapidly activate various signal transduction pathways that could participate in estrogen-mediated regulation of synaptic plasticity. Although the mechanisms underlying these effects are not clearly understood, it has been repeatedly suggested that they involve a plasma membrane receptor which has direct links to several intracellular signaling cascades. To further address the question of whether E2 acts directly at the synapse and through membrane-bound receptors, we studied the effects of E2 and of ligands of estrogen receptors on various signaling pathways in cortical synaptoneurosomes. Our results demonstrate that E2 elicits N-methyl-D-aspartate receptor phosphorylation and activates the extracellular signal-regulated kinase and the phosphatidylinositol 3-kinase/Akt signal transduction pathways in this cortical membrane preparation. Furthermore, we provide evidence for the presence of a membrane-bound estrogen receptor responsible for these effects in cortical synaptoneurosomes. Our study demonstrates that E2 directly acts at cortical synapses, and that synaptoneurosomes provide a useful system to investigate the mechanisms by which E2 regulates synaptic transmission and plasticity.
Dominguez
Reymundo
R
Neuroscience Program, University of Southern California, Los Angeles, California, USA.
Liu
Roulan
R
Baudry
Michel
M
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D011960:Receptors, Estrogen; D016194:Receptors, N-Methyl-D-Aspartate; D004958:Estradiol; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases