NMDA receptor type 2D gene as target for estrogen receptor in the brain

Although it is well known that estrogen exerts its effect in the brain, the direct target genes transcriptionally regulated by estrogen or rather estr ogen receptor (ER) are almost unknown. During the search for estrogen recep tor-binding sites from human CpG island Library, we found one genomic DNA f ragment corresponding to the putative 3'-untranslated region of human NMDA receptor subunit 2D (NR2D) gene. It contained at least four half palindromi c estrogen responsive elements (hEREs) within two hundred nucleotides, whic h was conserved also in the rat. Interestingly, the NR2D mRNA is co-localiz ed with ER alpha and/or ER beta mRNA in a number of regions of rat brain. W e have also demonstrated that NR2D mRNA is up-regulated in rat hypothalamus by estrogen possibly via hEREs identified here. Thus, we suggest that NR2D is one of the direct targets of estrogen receptors which are involved in r eproductive as well as non-reproductive actions in the brain. (C) 1999 Else vier Science B.V. All rights reserved.