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Novel Target Sites for Estrogen Action in the Dorsal Hippocampus: An Examination of Synaptic Proteins¹

Laboratory of Neuroendocrinology (W.G.B., S.E.A., J.C.D., S.J.L., K.B., B.S.M.) and Laboratory of Molecular and Cellular Neuroscience (P.B.A., P.G.), The Rockefeller University, New York, New York 10021

Address all correspondence and requests for reprints to: Wayne Brake, Ph.D., Laboratory of Neuroendocrinology, Box 165, The Rockefeller University, 1230 York Avenue, New York, New York 10021. E-mail: brakew{at}mail.rockefeller.edu

Structural studies have shown that estrogens increase dendritic spine number in the dorsal CA1 field of rat hippocampus using Golgi impregnation as well as the number of dorsal CA1 synapses visualized via electron microscopy. The present study was carried out to further these findings by examining changes in the levels of pre- and postsynaptic proteins using radioimmunocytochemistry (RICC). In this study, 2 days of estradiol-benzoate treatment produced significant and comparable increases in synaptophysin, syntaxin, and spinophilin immunoreactivity (IR) in the CA1 region of the dorsal hippocampus of ovariectomized female rats. For spinophilin, IR was also increased in the hilar region of the dentate gyrus as well as CA3. In all cases, the nonsteroidal estrogen antagonist CI628, which has been previously shown to block spine formation, inhibited the effects of estrogen. However, these protein differences were not detected in whole hippocampus using Western blots. These findings add to a growing body of evidence that estrogens increase synapses in the CA1 region of hippocampus along with changes in previously unidentified sites. These results also suggest that RICC is a rapid and sensitive method for examining molecular changes in synaptic profiles in anatomically distinct brain regions.