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• W1965401973 abstract "Tyrosine hydroxylase (TH) promoter activity is induced by 17beta-estradiol (E(2)) in PC12 cells expressing estradiol receptor-alpha (ERalpha) requiring a cAMP/calcium response element (CRE/CaRE) at -45. To examine whether membrane-initiated estradiol signaling is underlying this induction, cells co-transfected with TH reporter construct and ERalpha expression vector were exposed to membrane-impermeant estradiol conjugate (beta-estradiol-6-(O-carboxy-methyl) oxime-bovine serum albumin, E(2)BSA). TH promoter activity was elevated by E(2)BSA in dose- and time-dependent manner. E(2)BSA also elicited rapid phosphorylation of CRE binding protein (CREB) and increased CRE-driven promoter activity. Over-expression of dominant negative forms of CREB, with mutations in DNA binding or phosphorylation site, prevented TH promoter response to E(2)BSA. Pre-treatment with protein kinase A (PKA) and MEK inhibitors reduced E(2) dependent phosphorylation of CREB and ERK, and also decreased induction of TH promoter activity by E(2) or E(2)BSA. Blocking S-palmitoylation of ERalpha with C451A mutation and/or pre-treatment with 2-Bromopalmitate did not prevent but instead enhanced E(2) or E(2)BSA-elicited induction of TH promoter activity. These findings reveal, for the first time, that estradiol induction of TH gene transcription with ERalpha in PC12 cells involves membrane-initiated estradiol signaling, rapid activation of dual PKA/MEK signaling pathways, leading to CREB phosphorylation, acting at CRE/CaRE. The data demonstrate possible mechanism whereby estradiol affects catecholaminergic systems in vivo." @default.
• W1965401973 created "2016-06-24" @default.
• W1965401973 creator A5031670347 @default.
• W1965401973 creator A5067263435 @default.
• W1965401973 creator A5068786280 @default.
• W1965401973 date "2010-01-01" @default.
• W1965401973 modified "2023-10-15" @default.
• W1965401973 title "Membrane-initiated estradiol signaling increases tyrosine hydroxylase promoter activity with ERα in PC12 cells" @default.
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• W1965401973 doi "https://doi.org/10.1111/j.1471-4159.2009.06430.x" @default.
• W1965401973 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19818101" @default.
• W1965401973 hasPublicationYear "2010" @default.
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