Transcription profiling of estrogen target genes in young and old mouse uterus.
The goal of this study was to identify age-related changes in the expression of estrogen target genes in mouse uterus. We developed a novel 'estrogen response element (ERE) Chip' microarray bearing 297 genes including both known estrogen target genes and genes identified by searching the mouse genome database to have EREs, AP-1 sites, and Sp1 sites, all targets of estrogen receptor (ER) regulation. 400-500 bp PCR products of these 297 genes were printed onto nylon membranes creating the 'ERE Chip' microarray. This microarray is unique because it is the first estrogen-responsive gene-specific microarray to identify changes in uterine gene expression in young versus old mice. Using this ERE microarray we identified 10 uterine genes whose expression was up-regulated in old mice, e.g. beta-actin, calcium binding protein 45a, Sp1, and COUP-TFII. In contrast, the expression of only 4 uterine genes, i.e., complement C3, lactoferrin, Muc-1, and 17-beta-hydroxysteroid dehydrogenase 8 (H2-Ke6) was down-regulated in old mice. These changes may reflect an increase in stromal and a decrease in glandular epithelial gene expression, and may be associated with age-related changes in these tissue compartments within the uterus, possibly leading to the decline in reproductive function in C57Bl/6 mice.
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, 570 South Preson St Baxter Building RM. 304, Louisville, KY 40292, USA.
Abdelnaby
A
Khalyfa
Carolyn M
CM
Klinge
William C
WC
Hall
Xuechun
X
Zhao
Marilyn M
MM
Miller
Eugenia
E
Wang
D000375:Aging / Q000235:genetics*; D000818:Animals; D004967:Estrogens / Q000235:genetics / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014599:Uterus / Q000378:metabolism / Q000502:physiology*
D004967:Estrogens; D012097:Repressor Proteins