Differential expression patterns of Wnt and beta-catenin/TCF target genes in the uterus of immature female rats exposed to 17alpha-ethynyl estradiol

• Published in: Toxicological sciences Vol. 91; no. 2; pp. 419 - 430
• Main Authors: Katayama, Seiichi, Ashizawa, Koji, Fukuhara, Tadahiro, Hiroyasu, Makoto, Tsuzuki, Yasuhiro, Tatemoto, Hideki, Nakada, Tadashi, Nagai, Kenji
• Format: Journal Article
• Language: English
• Published: United States 01-06-2006
• Subjects: Animals; beta Catenin - genetics; beta Catenin - metabolism; Estrogens - pharmacology; Ethinyl Estradiol - pharmacology; Female; Gene Expression Profiling; Gene Expression Regulation - drug effects; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Rats; Rats, Inbred Strains; RNA, Messenger - metabolism; TCF Transcription Factors - genetics; TCF Transcription Factors - metabolism; Uterus - drug effects; Uterus - metabolism; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt-5a Protein; Wnt4 Protein
• ISSN: 1096-6080

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 17alpha-ethynyl estradiol (EE, 3 mug/kg), a potent ER agonist. We focused on four categories of sex steroid hormone receptor genes: well-known estrogen target genes, Wnt genes, and beta-catenin/T-cell factor (TCF) target genes. ERalpha, ERbeta, 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 beta-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 beta-catenin/TCF target genes in the uterus of immature rats, indicating that their molecules are the potential players affected by estrogenic stimuli.