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PMID: 7479947 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Identification of a putative estrogen response element in the gene encoding brain-derived neurotrophic factor.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 24 ·1995-11-21 ·Pages 11110-4

Sohrabji F, Miranda RC, Toran-Allerand CD

Abstract

We have been studying the role and mechanism of estrogen action in the survival and differentiation of neurons in the basal forebrain and its targets in the cerebral cortex, hippocampus, and olfactory bulb. Previous work has shown that estrogen-target neurons in these regions widely coexpress the mRNAs for the neurotrophin ligands and their receptors, suggesting a potential substrate for estrogen-neurotrophin interactions. Subsequent work indicated that estrogen regulates the expression of two neurotrophin receptor mRNAs in prototypic peripheral neural targets of nerve growth factor. We report herein that the gene encoding the neurotophin brain-derived neurotrophic factor (BDNF) contains a sequence similar to the canonical estrogen response element found in estrogen-target genes. Gel shift and DNA footprinting assays indicate that estrogen receptor-ligand complexes bind to this sequence in the BDNF gene. In vivo, BDNF mRNA was rapidly up-regulated in the cerebral cortex and the olfactory bulb of ovariectomized animals exposed to estrogen. These data suggest that estrogen may regulate BDNF transcription, supporting our hypothesis that estrogen may be in a position to influence neurotrophin-mediated cell functioning, by increasing the availability of specific neurotrophins in forebrain neurons.

MeSH Terms
Animals Base Sequence Brain-Derived Neurotrophic Factor Cerebral Cortex/physiology Estrogens/physiology Female Gene Expression Regulation Genes Molecular Sequence Data Nerve Tissue Proteins/genetics Olfactory Bulb/physiology Ovariectomy Promoter Regions, Genetic RNA, Messenger/genetics Rats Transcription, Genetic/drug effects
Chemicals
Brain-Derived Neurotrophic Factor Estrogens Nerve Tissue Proteins RNA, Messenger
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sohrabji F
Department of Anatomy and Cell Biology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Miranda R C
Toran-Allerand C D
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.24.11110
Published
1995-11-21
Pages
11110-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC40581
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.92.24.11110 PMC Full Text View journal details
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