Estrogen: mechanisms for a rapid action in CA1 hippocampal neurons.
Estrogen modulates a variety of functions, most of which can be explained by the classical genomic mechanism of action. However, a number of estrogen's actions appear to be incompatible with this mechanism and fall into the category of nongenomic. In the hippocampus, application of 17beta-estradiol rapidly enhances the amplitude of kainate-induced currents of CA1 neurons. The potentiation resulted from a cyclic adenosine monophosphate-dependent phosphorylation process rather than a direct allosteric modulation of AMPA/kainate receptors. To initiate this potentiation, estrogen is required on both sides of the plasma membrane. Extracellularly, estrogen appears to activate a G-protein-coupled receptor, whereas the intracellular action of estrogen appears to be a modulation of the balance between phosphorylation and dephosphorylation. The binding sites responsible for the potentiation are genetically or pharmacologically distinct from both estrogen receptors alpha and beta. These findings provide support for the concept of a novel mechanism of action for estrogen.
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004967:Estrogens / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007608:Kainic Acid / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011960:Receptors, Estrogen / Q000502:physiology