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) mess enger RNAs have been detected in the hippocampus, the presence of functiona l protein remains uncertain. The present study used a new radiolabeled estr ogen, [I-125]estrogen, and in vivo autoradiography to address this question . Nuclear uptake and retention of [I-125]estrogen was detected in the pyram idal cells of CA1-CA3, with the majority of cells in the ventral horn of CA 2 and CA3 being labeled. Additional labeled cells were scattered throughout the strata oriens and radiatum and the hilus of the dentate gyrus. Since t he number and distribution of labeled cells in the hippocampus was more tha n expected, in situ hybridization was used to assess the localization of es trogen receptor (alpha and beta) messenger RNAs in this brain region. The r esults revealed that both estrogen receptors are expressed in regions where [I-125]estrogen binding was seen, although the intensity of estrogen recep tor-alpha hybridization signal appears to be stronger when compared with es trogen receptor-beta. The results of these studies have demonstrated the presence of estrogen rec eptors 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 abou t steroid hormones and their mechanism(s) of action in a region associated with learning and memory and affected by the neurodegenerative conditions o f aging. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reser ved.