Abstract
Objective: The early response genes induced by 17β-estradiol(E2) include the important regulatory genes, such as transcription factors. The aim of this study was to investigate the early response gene induced by E2 in the ovariectomized(Ovx) mouse uterus. Design: Experimental laboratory study using a mouse model. Materials and Methods: The Ovx mice were treated with a single s.c injection of E2(300ng/0.1ml/mouse) dissolved in sesame oil, while the control mice received oil only. They were given the pure antiestrogen ICI 182,780(500ng/mouse) 30min before the injection of E2. The Ovx mice were killed at 2, 4, 6 and 12 hr after the injection, and their uteri were collected for RNA extraction. The expression of the 15 transcription factors was examined by reverse transcription-polymerase chain reaction(RT-PCR).The localization of these protein was investigated by immunohistochemistry. Results: The expression patterns of genes were divided into four groups: Group I, early response genes include Fra1, Fra2, CREB2 and GATA5; Group II, response maintained genes include CREB1, ATF1, GLI3 and E2F3; Group III, late response genes include E2F1; Group IV, down regulated genes include GLI1, GLI2, E2F5, GATA2, GATA3 and GATA6. Among these early resposne genes, the Fra1 and Fra2 were selected for protein localization. The levels of Fra1 mRNA peaked 2.3-fold at 4 hr, the levels of Fra2 mRNA peaked 3.2-fold at 2 hr compared with the control values, respectively and these mRNA levels returned to basal levels at 12 hr. In addition, The ICI 182,780 clearly blocked the effect of E2. The expression of Fra1 and Fra2 protein was stronger in the myometrium than in other regions. Conclusion: The results of this study suggest that expression of the Fra1 and Fra2 mRNA is up-regulated by E2 and activated via an estrogen nuclear receptor in the mouse uterus and these protein may play an important role in mediating the contraction and relaxation of the uterine smooth muscle, but the functional significance of these protein in the myometrium is not clear.
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