Cooperation of Genomic and Rapid Nongenomic Actions of Estrogens in Synaptic Plasticity.

Neuroplasticity refers to the changes in the molecular and cellular processes of neural circuits that occur in response to environmental experiences. Clinical and experimental studies have increasingly shown that estrogens participate in the neuroplasticity involved in cognition, behavior, and memory. It is generally accepted that estrogens exert their effects through genomic actions that occur over a period of hours to days. However, emerging evidence indicates that estrogens also rapidly influence the neural circuitry through nongenomic actions. In this review, we provide an overview of the genomic and nongenomic actions of estrogens and discuss how these actions may cooperate in synaptic plasticity. We then summarize the role of epigenetic modifications, synaptic protein synthesis, and posttranslational modifications, and the splice variants of estrogen receptors in the complicated network of estrogens. The combination of genomic and nongenomic mechanisms endows estrogens with considerable diversity in modulating neural functions including synaptic plasticity.