Ultrastructural localization of estrogen receptor β immunoreactivity in the rat hippocampal formation

Several lines of evidence indicate that estrogen affects hippocampal synaptic plasticity through rapid nongenomic mechanisms, possibly by binding to plasma membrane estrogen receptors (ERs). We have previously shown that ER alpha immunoreactivity (ir) is in select interneuron nuclei and in several extranuclear locations, including dendritic spines and axon terminals, within the rat hippocampal formation (Milner et al., [2001] J Comp, Neurol 429:355). The present study sought to determine the cellular and subeellular locations of ER beta-ir. Coronal hippocampal sections from diestrus rats were immunolabeled with antibodies to ER beta and examined by light and electron microscopy. By light microscopy, ER beta-ir was primarily in the perikarya. and proximal dendrites of pyramidal and granule cells. ER beta-ir was also in a few nonprincipal cells and scattered nuclei in the ventral subiculum and CA3 region. Ultrastructural analysis revealed ER beta-ir at several extranuclear sites in all hippocampal subregions. ER beta-ir was affiliated with cytoplasmic organelles, especially endomembranes and mitochondria, and with plasma membranes primarily of principal cell perikarya and proximal dendrites. ER beta-ir was in dendritic spines, many arising from pyramidal and granule cell dendrites. In both dendritic shafts and spines, ER beta-ir was near the perisynaptic zone adjacent to synapses formed by unlabeled terminals. ER beta-ir was in preterminal axons and axon terminals, associated with. clusters of small, synaptic vesicles. ER beta-labeled terminals formed both asymmetric and symmetric synapses with dendrites. ER beta-ir also was detected in glial profiles. The cellular and subcellular localization of ER beta-ir was generally similar to that of ERa, except that ER beta was more extensively found at extranuclear sites. These results suggest that ER beta may serve primarily as a nongenomic transducer of estrogen actions in the hippocampal formation.