Estrogen regulates cytoskeletal flexibility, cellular metabolism and synaptic proteins: A proteomic study

SummaryEstrogen (E2) influences brain function to induce gender differences in neuronal processes. In contrast to its well-described effects on signaling systems and gene transcription factors, our knowledge of E2-regulated protein networks is rather limited. Thus, we examined changes in protein expression patterns in the whole brains of ovariectomized mice after 24 h estrogen exposure using two-dimensional differential gel electrophoresis. Interpretation of our network-based hypothesis suggested that E2 regulates synaptic proteins and processes, increases cytoskeletal flexibility and alters glucose consumption in the brain. We verified the predicted reduced basal synaptic activity using in vivo microdialysis in conscious mice, showing that E2 decreases the extracellular concentrations of certain amino acids in two different brain areas (in the striatum and in the hypothalamus) and that this is independent from the E2 receptor densities. Our data reveal that E2 induces minor, but substantial changes to functionally different protein networks at the whole brain level, and as a cumulative effect, it adjusts the brain steady-state condition to a more flexible state.