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J.Health Sci., 54(5), 596-601, 2008

In Vivo Anti-estrogenic Effects of Menadione on Hepatic Estrogen-responsive Gene Expression in Male Medaka (Oryzias latipes)

Akemi Yamaguchi,a, b Shinya Kohra,b, c Hiroshi Ishibashi,d Koji Arizono,d and Nobuaki Tominaga*, a

aDepartment of Chemical and Biological Engineering, Ariake National College of Technology, 150 Higashihagio-machi, Omuta, Fukuoka 836-8585, Japan, bGraduate School of Science and Technology, Nagasaki University, cFaculty of Environmental Studies, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan, and dFaculty of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, 3-1-10 Tsukide, Kumamoto 862-8502, Japan

Menadione, a synthetic vitamin K3, exhibits antiestrogenic activity on in vitro assay. However, the in vivo anti-estrogenic effects of menadione have not been determined, while correlations between biological effects and structural changes are unclear. Thus, we investigated the in vivo anti-estrogenic activity of menadione under fluorescent light and dark conditions. Suppression of the hepatic estrogen response genes vitellogenin1 (VTG1), VTG2 and estrogen receptor-α (ER-α) was used as an index of antiestrogenic activity. Male medaka (Oryzias latipes) were treated with nominal concentrations of menadione in the presence or absence of 17β-estradiol (E2), and hepatic VTG1, VTG2 and ER-α mRNA levels were determined by quantitative real-time PCR. In the presence of E2 under dark conditions, expression of hepatic VTG2 and ER-α genes was suppressed by menadione treatment. On the other hand, menadione activity was lost under fluorescent light conditions. These results suggest that menadione has antiestrogenic activity in vivo, and that this activity is diminished under fluorescent light, probably due to a structural change in menadione.