Genome-wide analysis of changes in early gene expression induced by oestrogen.
BACKGROUND
The sex hormone 17beta-oestradiol (E2) has profound effects on many aspects of reproduction, development, as well as behaviour. Although the oestrogen receptor is well characterized on a molecular level, relatively few genes affected by E2 have been identified, and the mechanisms underlying the physiological changes caused by E2 are largely unknown. In order to identify oestrogen-regulated genes in vivo, early uterine gene expression profiles were developed using DNA microarrays.


RESULTS
Ovariectomized mice were exposed to 17beta-oestradiol for 6 h, and mRNA expression analysis for 9977 genes was performed. Although a large number of genes was affected by oestrogen administration, the genes that showed higher reproducibility in repetitive experiments were selected and further examined. For most of the selected genes, expression was induced in a dose-dependent manner, and gene expression was not altered following oestrogen treatment in oestrogen receptor-alpha (ER(alpha))-deficient mice. In combination with the estimation of gene expression levels using quantitative PCR, it was revealed that multiple genes related to sterol biosynthesis, tRNA synthesis, RNA processing, and growth signalling were activated. Based on the microarray data, we selected additional genes related to sterol biosynthesis and tRNA synthesis and confirmed that these genes are also activated by oestrogen.


CONCLUSIONS
Genes suggesting a basis for the drastic uterotrophic effect observed several days following oestrogen administration were identified. These findings not only reveal the diverse effect of oestrogen signalling on transcript levels in vivo but also demonstrate the ability of DNA microarrays to identify cellular pathways affected by oestrogen.
Watanabe
Hajime
H
Center for Integrative Bioscience and Core Research for Evolutional Science and Technology, Okazaki National Research Institutes, 38 Nishigonaka, Myoudaiji, Okazaki, Aichi 444-8585, Japan.
Suzuki
Atsuko
A
Mizutani
Takeshi
T
Khono
Satomi
S
Lubahn
Dennis B
DB
Handa
Hiroshi
H
Iguchi
Taisen
T
D000818:Animals; D004958:Estradiol / Q000008:administration & dosage / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D016678:Genome; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014599:Uterus / Q000502:physiology*
D004958:Estradiol