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

Abstract

Menadione, a synthetic vitamin K3, exhibits anti-estrogenic 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 anti-estrogenic 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 anti-estrogenic activity in vivo, and that this activity is diminished under fluorescent light, probably due to a structural change in menadione.