Induction of the estrogen-responsive genes encoding choriogenin H and L in the liver of male medaka (Oryzias latipes) upon exposure to estrogen receptor subtype-selective ligands

Choriogenin (Chg) H and L are estrogen-induced chorion precursors. We measured the induction of ChgH and ChgL mRNA in the livers of male medaka fish treated with Orthoester-2k, a selective ligand for estrogen receptor (ER) α, and 2-(4-hydroxyphenyl)-5-hydroxy-1,3-benzoxazole (HPHB), a selective ligand of ERβ. Although both ChgH and ChgL mRNA were induced by treatment with Orthoester-2k or HPHB separately, their combination induced much greater expression of each Chg. ChgH expression correlated more closely with Orthoester-2k dosage when combined with a small fixed dose of HPHB (1 μm), whereas ChgL mRNA expression was more responsive to HPHB dose when combined with a fixed dose of Orthoester-2k (2.8 nm). Moreover, upon long-term treatment with Orthoester-2k, ChgH mRNA and ERα mRNA expression showed similar patterns with peak expression between days 6 and 10. These results imply that ERβ primarily regulates ChgL mRNA expression and ERα action primarily regulates ChgH mRNA expression. Thus, it is necessary to develop screening methods for fish ER subtype-specific ligands.