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 ERα and ERβ. In this paper, we measured VTG1 and VTG2 mRNA induction in male medaka liver, which was treated with ERα-selective ligand, (17α, 20E)-3-hydroxy-17,20-[(1-methoxyethylidene)bis(oxy)]-19norpregna-1,3,5(10),20-tetraene-21-carboxylic acid, methyl ester or ERβ-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 ERα-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, ERβ-selective ligands significantly increased VTG2 mRNA in the presence of ERα 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 ERα. In contrast, VTG2 expression is regulated by both ERα and ERβ, with ERα being essential for VTG2 gene expression and ERβ being essential for enhancement.