RRC ID 62727
Author Takeo C, Ikeda K, Horie-Inoue K, Inoue S.
Title Identification of Igf2, Igfbp2 and Enpp2 as estrogen-responsive genes in rat hippocampus.
Journal Endocr J
Abstract Estrogen has an important effect on higher brain function such as memory, learning, and emotion in which the hippocampus plays a critical role. The hippocampus expresses estrogen receptors, ER alpha and ERbeta, which are ligand-dependent transcription factors; however, the precise mechanism of estrogen action is not fully understood. We explored genes which are up-regulated by estrogen in the hippocampus using ovariectomized rat models. Microarray analysis revealed that mRNA levels of ectonucleotide pyrophosphatase/phosphodiesterase 2 (Enpp2), insulin like growth factor 2 (Igf2) and insulin-like growth factor binding protein 2 (Igfbp2) were increased by estrogen in the hippocampus. Quantitative-PCR analysis demonstrated that the levels of Enpp2, Igf2 and Igfbp2 mRNA were elevated by estrogen administration in the hippocampus but not in the hypothalamus. On the other hand, ERalpha, ERbeta and progesterone receptor (PR) mRNA expression was up-regulated by estrogen only in the hypothalamus. We further analyzed the time-dependent regulation of these genes using rat pituitary adenoma, MtT/S and GH3 cells, which are known to express ERalpha. In both MtT/S and GH3 cells, Igfbp2 and Enpp2 mRNAs were up- and down-regulated by estrogen, respectively, whereas Igf2 mRNA was increased only in GH3 cells. These results demonstrate a brain region- and cell type-specific responses to estrogen in rat brain, suggesting that Igf signaling may mediate the estrogen function in the hippocampus.
Volume 56(1)
Pages 113-20
Published 2009-1-1
DOI 10.1507/endocrj.k08e-220
PII JST.JSTAGE/endocrj/K08E-220
PMID 18946176
MeSH Animals Cell Line Estradiol / pharmacology* Female Gene Expression Profiling Gene Expression Regulation / drug effects Hippocampus / drug effects* Hippocampus / metabolism Insulin-Like Growth Factor Binding Protein 2 / genetics* Insulin-Like Growth Factor Binding Protein 2 / metabolism Insulin-Like Growth Factor II / genetics* Insulin-Like Growth Factor II / metabolism Oligonucleotide Array Sequence Analysis Organ Specificity / drug effects Organ Specificity / genetics Phosphoric Diester Hydrolases / genetics* Phosphoric Diester Hydrolases / metabolism Pituitary Gland / drug effects Pituitary Gland / metabolism Pyrophosphatases / genetics* Pyrophosphatases / metabolism Rats Rats, Wistar Receptors, Estrogen / genetics Receptors, Estrogen / metabolism Receptors, Progesterone / genetics Signal Transduction / drug effects Signal Transduction / genetics
IF 1.952
Human and Animal Cells MtT/S(RCB0528)