Estradiol alters transcription factor gene expression in primate prefrontal cortex.
Estrogen protects neurons from a variety of experimental insults in vitro, and is thought to protect from acute and chronic neurodegenerative processes in vivo. Estrogen also enhances higher-level cognitive functions that are centered in the dorsolateral prefrontal cortex (DLPFC) in human and non-human primates. To investigate genomic mechanisms involved in estrogenic effects on the primate brain in vivo, we compared transcription factor mRNA and protein expression in the DLPFC of ovariectomized rhesus monkeys treated with either vehicle or estradiol (E2). c-FOS, E2F1, and general transcription factor IIB (TFIIB) mRNA and protein expression were altered significantly by short-term E2 treatment, as shown by DNA array, in situ hybridization, and immunohistochemical and immunoblot evaluations. C-FOS expression was increased significantly whereas E2F1 and TFIIB levels were decreased in the DLPFC of E2-treated animals. These transcription factors were concentrated in cortical pyramids, as were estrogen receptors alpha and beta. These data indicate that estrogen may have direct as well as indirect effects on neuronal gene expression in the primate prefrontal cortex.
Wang
J
J
Developmental Endocrinology Branch, National Institute of Child Health, Bethesda, Maryland, USA.
Cheng
C M
CM
Zhou
J
J
Smith
A
A
Weickert
C Shannon
CS
Perlman
W R
WR
Becker
K G
KG
Powell
D
D
Bondy
C A
CA
D000818:Animals; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D004958:Estradiol / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008253:Macaca mulatta; D009474:Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D035581:Transcription Factor TFIIB / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D035581:Transcription Factor TFIIB; D014157:Transcription Factors; D004958:Estradiol