Time- and dose-dependent differential upregulation of three genes by 17 beta-estradiol in endothelial cells.
The purpose of this study was to identify genetic targets in the vasculature for estrogen by profiling genes expressed in female human aortic endothelial cells exposed to various doses of 17 beta-estradiol at differing concentrations and for differing periods of time. Our approach employed a RT-PCR-based cloning strategy of DNA differential display analysis, with differential expression verified by semiquantitative PCR performed with gene-specific primers. A significant increase in mRNA expression in response to 17 beta-estradiol was observed for the following three genes: aldose reductase (3.4-fold), caspase homologue-alpha protein (4.2-fold), and plasminogen activator inhibitor-1 intron e (2.3-fold). For all three upregulated genes, estradiol-induced upregulation occurred with a similar time course and temporally clustered to the first 24 h after hormone treatment. In addition, the effect of estradiol dose on gene expression was consistent and occurred at physiological concentrations. Our results describe previously uncharacterized estradiol-sensitive time- and dose-dependent regulation of genes with potential importance to vascular function in human endothelial cells.
Villablanca
Amparo C
AC
Division of Cardiovascular Medicine, University of California, Davis, California 95616-8636, USA. avillalanca@ucdavis.edu
Lewis
Kristine A
KA
Rutledge
John C
JC
D000449:Aldehyde Reductase / Q000235:genetics*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D013997:Time Factors
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D047908:Intracellular Signaling Peptides and Proteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D004958:Estradiol; D000449:Aldehyde Reductase; D003546:Cysteine Endopeptidases