Evidence for novel estrogen binding sites in the rat hippocampus.

Estrogen modulates the morphology and physiology of the rat hippocampus and enhances cognitive function. While estrogen receptor (alpha and beta) messenger RNAs have been detected in the hippocampus, the presence of functional protein remains uncertain. The present study used a new radiolabeled estrogen, [125I]estrogen, and in vivo autoradiography to address this question. Nuclear uptake and retention of [125I]estrogen was detected in the pyramidal cells of CA1-CA3, with the majority of cells in the ventral horn of CA2 and CA3 being labeled. Additional labeled cells were scattered throughout the strata oriens and radiatum and the hilus of the dentate gyrus. Since the number and distribution of labeled cells in the hippocampus was more than expected, in situ hybridization was used to assess the localization of estrogen receptor (alpha and beta) messenger RNAs in this brain region. The results revealed that both estrogen receptors are expressed in regions where [125I]estrogen binding was seen, although the intensity of estrogen receptor-alpha hybridization signal appears to be stronger when compared with estrogen receptor-beta.The results of these studies have demonstrated the presence of estrogen receptors in rat hippocampus and shown that the distribution of binding sites was much greater than expected, particularly in the pyramidal cells of the ventral hippocampus. These observations challenge our current thinking about steroid hormones and their mechanism(s) of action in a region associated with learning and memory and affected by the neurodegenerative conditions of aging.