Estrogen produced in cultured hippocampal neurons is a functional regulator of a GABAergic machinery.
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.
Ikeda
Takamitsu
T
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
Matsuki
Norio
N
Yamada
Maki K
MK
D000818:Animals; D001141:Aromatase / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism*; D000077267:Fulvestrant; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D007527:Isoenzymes / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013629:Tamoxifen / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D004965:Estrogen Antagonists; D004967:Estrogens; D007527:Isoenzymes; D012333:RNA, Messenger; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; D005680:gamma-Aminobutyric Acid; D001141:Aromatase; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2