Elucidation of the multifunctional signaling of estrogen using the visualization of estrogen responsible neurons

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Estrogen plays an essential role for reproduction, plasticity and neuroprotection to affect on the central nervous system. The purpose of the present study is to examine the mechanisms of estrogen action using the visualized neurons that are responsible to estrogen in the estrogen receptor gene promoter transgenic rats. Most important result is that EGFP expression under the control of estrogen receptor gene promoter is a specific marker for the sexually dimorphic nucleus of the preoptic area. Because sexual dimorphism of this nucleus is established by estrogen during the perinatal period, the new, live marker would contribute to clarify the molecular mechanisms of the sexual differentiation. On the other hand, EGFP expression is observed in the hippocampus that is noted function of estrogen for the plasticity and neurogenesis. We determined acute and chronic effects of physiological concentration of estrogen on the outward potassium currents in the primary cultured EGFP hippocampal neurons. Immature neurons showed the facilitated effect of 48 h treatment of estrogen, however, mature neurons exhibited the suppressive effect on the outward potassium currents. After the 48 h treatment of estrogen, bath application of 250 pM estrogen enhanced the potassium currents. These results suggest that estrogen influence the development and excitability of hippocampal neurons. One more thing to be noted is that there is the sex difference in the number of EGFP expressed cells in the area postrema and the nucleus tractus solitarius that are known to play an important role for cardiovascular regulation. Because hypertension is inhibited by estrogen in female, we could expect to clear the mechanisms of estrogen function on the cardiovascular regulation. Thus, we can show a number of the important results and we would like to study further to make clear the molecular mechanisms of estrogen function in the central nervous system.