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Estrogens are accumulating in environment and their effects on a variety of reproductive processes and tumorigenesis were reported by previous study, but the mechanism of estrogen promoting neoplasia was still not clear. F-box protein (FBP) is the component of E3 ubiquitin ligase which takes part in a variety of key biological processes. In this study, using mature male zebrafish, which are more sensitive to estrogen treatment, we examined influence of 17α-ethinylestradiol (EE2) exposure on the expression of a series of hepatic FBP genes, which take part in a variety of biological processes, including tumorigenesis. The influence of EE2 on the expression of hepatic mRNA concentrations of FBP genes were quantified based on the expression of the optimal intal control gene in male zebrafish after 7-day exposure to EE2, from a low-dose concentration (1 ng/L) to environmentally relevant concentrations (10, 100ng/L). Our results showed that EE2 exposure reduced the expression of fbxll4a, fbxll4b, fbxo25 and β-TRCP2b, but enchanced the expression of skp2. While the alterations in fbxl2, fbxw7,fbxo9, β-TRCP2a, fbxll8 and fbxo45 mRNA levels were not observed after EE2 exposure. Thus, our results showed that the expression of hepatic FBP genes exhibited differentially in male zebrafish exposed EE2. The changes of the expression level of FBP genes induced by EE2 may be an important clue to elucidate the correlations of estrogen and hepatic tumors.