Expression Analysis of Estrogen-responsive Genes Vitellogenin 1 and 2 in Liver of Male Medaka (Oryzias latipes) Exposed to Selective Ligands of Estrogen Receptor Subtypes

Vitellogenin (VTG) is a useful biomarker for detecting the estrogenic activity of chemicals in aquatic environments. However, little information is available on the regulatory mechanisms of the expression of each VTG subtype, particularly the relationship between expression patterns of VTG1/2 and estrogen receptor (ER) subtypes, such as ER alpha and ER beta. In this paper, we measured VTG1 and VTG2 mRNA induction in male medaka liver, which was treated with ER alpha-selective ligand, (17 alpha, 20E)-3-hydroxy-17.20-[(1-methoxyethylidene)bis(oxy)]-19-norpregna-1,3,5(10),20-tetraene-21-carboxylic acid, methyl ester or EM-selective ligand, 2-(4-hydroxyphenyl)-5-hydroxy-1,3-benzoxazole and investigated the characteristics of ER subtype function in VTG1 and VTG2 inductions. Hepatic VTG1 mRNA was induced by ERa-selective ligands at even low concentration and maximum increases were the same as for E2. VTG2 mRNA was also increased, but its levels were very low. On the other hand, ER alpha-selective ligands significantly increased VTG2 mRNA in the presence of ER alpha agonists. These results indicate that the expression of each VTG subtype is regulated by unique ER subtypes. VTG1 expression is only regulated by the action of ER alpha. In contrast, VTG2 expression is regulated by both ER alpha and ER beta, with ER alpha being essential for VTG2 gene expression and ER beta being essential for enhancement.