PMID- 17044036 OWN - NLM STAT- MEDLINE DCOM- 20070313 LR - 20181201 IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 84 IP - 8 DP - 2006 Dec TI - Estrogen produced in cultured hippocampal neurons is a functional regulator of a GABAergic machinery. PG - 1771-7 AB - Accumulating evidence suggests that estrogen is produced locally by the neurons in the brain. We observed that a 48-hr treatment with the estrogen receptor antagonists ICI 182780 and tamoxifen decreased the level of glutamate decarboxylase (GAD)-65, a rate-limiting gamma-aminobutyric acid (GABA)-synthesizing enzyme, in a dissociated hippocampal neuronal culture. Aromatase is an essential enzyme for estrogen biosynthesis. Treatment with an aromatase inhibitor decreased the GAD 65 level, indicating that estrogen biogenesis functions to maintain the level of this enzyme for GABAergic neurotransmission. Furthermore, insofar as the effect of ICI 182780 was observed equivalently in the presence of either brain-derived neurotrophic factor (BDNF) or BDNF-receptor inhibitor K252a, estrogen probably regulates GAD level independently of brain-derived neurotrophic factor (BDNF). Thus, estrogen produced by neurons is considered to be an intrinsic regulatory factor for neuronal networks that maintain GABAergic neurotransmission. FAU - Ikeda, Takamitsu AU - Ikeda T AD - Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan. FAU - Matsuki, Norio AU - Matsuki N FAU - Yamada, Maki K AU - Yamada MK LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Estrogen Antagonists) RN - 0 (Estrogens) RN - 0 (Isoenzymes) RN - 0 (RNA, Messenger) RN - 094ZI81Y45 (Tamoxifen) RN - 22X328QOC4 (Fulvestrant) RN - 4TI98Z838E (Estradiol) RN - 56-12-2 (gamma-Aminobutyric Acid) RN - EC 1.14.14.1 (Aromatase) RN - EC 4.1.1.15 (Glutamate Decarboxylase) RN - EC 4.1.1.15 (glutamate decarboxylase 2) SB - IM MH - Animals MH - Aromatase/pharmacology MH - Cells, Cultured MH - Dose-Response Relationship, Drug MH - Drug Interactions MH - Embryo, Mammalian MH - Estradiol/analogs & derivatives/pharmacology MH - Estrogen Antagonists/pharmacology MH - Estrogens/*metabolism MH - Fulvestrant MH - Gene Expression/drug effects MH - Gene Expression Regulation/drug effects MH - Glutamate Decarboxylase/metabolism MH - Hippocampus/*cytology MH - Immunohistochemistry/methods MH - Isoenzymes/metabolism MH - Neurons/*metabolism MH - RNA, Messenger/biosynthesis MH - Rats MH - Reverse Transcriptase Polymerase Chain Reaction/methods MH - Tamoxifen/pharmacology MH - gamma-Aminobutyric Acid/*metabolism EDAT- 2006/10/18 09:00 MHDA- 2007/03/14 09:00 CRDT- 2006/10/18 09:00 PHST- 2006/10/18 09:00 [pubmed] PHST- 2007/03/14 09:00 [medline] PHST- 2006/10/18 09:00 [entrez] AID - 10.1002/jnr.21083 [doi] PST - ppublish SO - J Neurosci Res. 2006 Dec;84(8):1771-7. doi: 10.1002/jnr.21083.