DISTRIBUTION AND HORMONE REGULATION OF ESTROGEN-RECEPTOR IMMUNOREACTIVE CELLS IN THE HIPPOCAMPUS OF MALE AND FEMALE RATS

Estrogen regulates the synaptic plasticity and physiology of the hippo campus as well as learning behaviors that are mediated by the hippocam pus. The density of dendritic spines and synapses, the number of N-met hyl-D-aspartate (NMDA) binding sites, the levels of NMDA receptor subu nit NR1 protein, muscimol binding to the gamma-amino butyric acid (GAB A)(A) receptor, and levels of glutamic acid decarboxylase message in t he CA1 region of the hippocampus are altered with estrogen treatment. In addition, some of these parameters exhibit sex differences in their response to estrogen treatment. To establish that estrogen can have a direct effect on the hippocampus and to determine whether or not sex differences in estrogen responsiveness are due to sex differences in e strogen receptor (ER) levels, we used immunocytochemistry with the AS4 09 antibody to map the location of ER-immunoreactive (ER-ir) cells in the hippocampus of male and female rats. We found that (1) the ERs app ear to be in interneurons rather than pyramidal or granule cell neuron s, (2) ER-ir cells are located in greatest concentration in the hilus of the dentate gyrus and the stratum radiatum of the CA1 region, (3) t he density of ER-ir cells exhibits a rostral to caudal gradient in the hilus and the CA1 regions, (4) there are no sex differences in either the number or immunostaining intensity of ER-ir cells in the hippocam pus, (5) the ER levels are down-regulated by estrogen in both male and female rats, and (6) the mean intensity of staining for the ER-ir cel ls in the hippocampus is about 25% of that in the ER-ir cells of the h ypothalamus. From this, we can conclude that estrogen can have a direc t effect on hippocampal neurons and that any sex differences in estrog en responsiveness is due to something other than sex differences in ER levels or function in the hippocampus. (C) 1997 Wiley-Liss, Inc.