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Physiol. Genomics 29: 13-23, 2007; doi:10.1152/physiolgenomics.00291.2005 Free Article
1094-8341/07 $8.00
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Received 24 November 2005; accepted in final form 21 November 2006.
Physiological Genomics 29:13-23 (2007)
1094-8341/07 $8.00 © 2007 American Physiological Society

Temporal analysis of E2 transcriptional induction of PTP and MKP and downregulation of IGF-I pathway key components in the mouse uterus

Mahinè Ivanga, Yvan Labrie, Ezequiel Calvo, Pascal Belleau, Céline Martel, Van Luu-The, Jean Morissette, Fernand Labrie and Francine Durocher

Oncology and Molecular Endocrinology Research Center, Centre Hospitalier de l'Université Laval (CHUL) Research Center, Centre Hospitalier Universitaire de Québec (CHUQ), Department of Anatomy and Physiology, Laval University, Quebec, Canada

17ß-Estradiol (E2) is well known to be associated with uterine cancer, endometriosis, and leiomyomas. Although insulin-like growth factor I (IGF-I) has been identified as a mediator of the uterotrophic effect of E2 in several studies, this mechanism is still not well understood. In the present study, identification of the genes modulated by a physiological dose of E2, in the uterus, has been done in ovariectomized mice using Affymetrix microarrays. The E2-induced genomic profile shows that multiple genes belonging to the IGF-I pathway are affected after exposure to E2. Two phases of regulation could be identified. First, from 0 to 6 h, the expression of genes involved in the cell cycle, growth factors, protein tyrosine phosphatases, and MAPK phosphatases is quickly upregulated by E2, while IGF-I receptor and several genes of the MAPK and phosphatidylinositol 3-kinase pathways are downregulated. Later, i.e., from 6 to 24 h, transporters and peptidases/proteases are stimulated, whereas defense-related genes are differentially regulated by E2. Finally, cytoarchitectural genes are modulated later. The present data show that a physiological dose of E2 induces, within 24 h, a series of transcriptional events that promote the uterotrophic effect. Among these, the E2-mediated activation of the IGF-I pathway seems to play a pivotal role in the uterotrophic effect. Furthermore, the protein tyrosine phosphatases and MAPK phosphatases are likely to modulate the estrogenic uterotrophic action by targeting, at different steps, the IGF-I pathway.

17ß-estradiol; 17ß-estradiol modulation; ovariectomized mice; oligonucleotide microarray; protein tyrosine phosphatase




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Proc. Natl. Acad. Sci. USAHome page
L. Zhu and J. W. Pollard
Estradiol-17beta regulates mouse uterine epithelial cell proliferation through insulin-like growth factor 1 signaling
PNAS, October 2, 2007; 104(40): 15847 - 15851.
[Abstract] [Full Text] [PDF]




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