ToxSci Advance Access originally published online on March 21, 2006
Toxicological Sciences 2006 91(2):419-430; doi:10.1093/toxsci/kfj167
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Differential Expression Patterns of Wnt and ß-Catenin/TCF Target Genes in the Uterus of Immature Female Rats Exposed to 17
-Ethynyl Estradiol
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* Kashima Laboratory, Mitsubishi Chemical Safety Institute Ltd., Kamisu, Ibaraki 314-0255, Japan; Science of Bioresource Production, The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima 890-0065, Japan; Laboratory of Animal Reproduction, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan; and Department of Bioproduction, Faculty of Agriculture, University of the Ryukyus, Nishihara-cho, Okinawa 903-0213, Japan
Received December 15, 2005; accepted March 13, 2006
To characterize the effects of an estrogen receptor (ER) agonist on the gene expressions in the uterus, immature female rats were administered once orally with 17
-ethynyl estradiol (EE, 3 µg/kg), a potent ER agonist. We focused on four categories of sex steroid hormone receptor genes: well-known estrogen target genes, Wnt genes, and ß-catenin/T-cell factor (TCF) target genes. ER, ERß, progesterone receptor, and androgen receptor mRNAs were all downregulated at 24 and/or 48 h after EE administration. Complement C3 and insulin-like growth factor 1 mRNAs were markedly induced after EE administration. Although the time courses of Wnt4, Wnt5a, and Wnt7a mRNA status varied until 12 h after EE administration, all of them were simultaneously downregulated at 24 and 48 h. The remarkable downregulation of Wnt7a mRNA in response to EE was considered to be important to understand the various uterine phenomena affected by ER agonists. In the ß-catenin/TCF target genes, the downregulation of anti-Mullerian hormone type 2 receptor and bone morphogenetic protein 4 mRNA after EE administration appeared to be closely related to the downregulation of Wnt7a. The upregulation of cyclin D1 and follistatin mRNA at the early phase after EE administration was considered to have been affected by the upregulation of Wnt4. These results indicate that an ER agonist influences not only the mRNA expression of sex steroid hormone receptor genes and well-known estrogen target genes but also Wnt genes (Wnt4, Wnt5a, Wnt7a) and ß-catenin/TCF target genes in the uterus of immature rats, indicating that their molecules are the potential players affected by estrogenic stimuli.
Key Words: estrogen receptor agonist; uterus; Wnt genes; ß-catenin/TCF target genes.
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