The gene motif of estrogen target has been found in the promoter of insulin, suggesting that estrogen can directly regulate insulin expression. Estrogen can also enhance insulin sensitivity by phosphorylating insulin receptors. These findings suggested that estrogen can regulate insulin production and signals. Some studies have indicated that the regulatory effect of estrogen on synaptic plasticity is mediated by ERb. Synaptic plasticity is one of the critical foundations in learning and memory. Estrogen is mainly generated from ovaries. Emerging studies have suggested that neurons can generate a minimal amount of estrogen, which may facilitate transient regulation of local brain metabolism. However, extensive studies must be performed to elucidate the functions of brain-derived estrogen. Both ERb and ERa have been observed in most brain regions. However, the functions of different receptors in learning and Cefpiramide sodium memory remain controversial. In present study, we found estrogen deficiency impaired the learning and memory mainly mediated by ERb in rats. The distribution of ERb in hippocampus of rat were modulated by the fluctuation of estrogen during oestrus cycle, but the ERa is a little changes in hippocampus during oestrus cycle, suggesting the ERb is more sensitive to estrogen fluctuation than the ERa in hippocampus. Further studyes have been suggested that ERb levels are greater than ERa in human and rat hippocampus. But contradiction with our results, Na Qu et al. showed that the expression of ERa, but not ERb, was decreased in the hippocampus starting 1 wk after ovariectomy. It is very difficult to interpreted this contradiction, may be due to ERa is more likely to be localized to the nucleus, at early stage of ovariectomy, ERa was implicated. Although the mechanisms by which estrogen Eliglustat Tartrate influences learning and memory are complicated and obscure, the present results suggested that estrogen deficiency can impair learning and memory mediated by ERb. These effects were associated with reduced insulin and glucose utilization.