title: Effects of synthetic polycyclic musks on estrogen receptor, vitellogenin, pregnane X receptor, and cytochrome P450 3A gene expression in the livers of male medaka (Oryzias latipes).
abstract: This study demonstrates the effects of synthetic polycyclic musks such as Galaxolide (HHCB), Tonalide (AHTN), Traseolide (ATII), Celestolide (ADBI), Phantolide (AHMI) and Cashmeran (DPMI), both on the early life stage and on gene expression in the livers of male medaka (Oryzias latipes). The toxicity ranking (the 96-h median lethal concentration) of the chemicals tested on 24-h-old medaka larvae descended in the order HHCB (0.95 mg/L)=ATII (0.95 mg/L)>AHTN (1.0 mg/L)>AHMI (1.2 mg/L)>ADBI (2.0 mg/L)>>DPMI (12 mg/L), indicating high acute toxicity of these compounds on the early life stages of medaka. Expression analysis of hepatic vitellogenin (VTG) protein showed potential estrogenic effects upon the addition of AHTN and HHCB, indicative of the induction of VTG synthesis in the livers of male medaka. We also investigated mRNA expression levels of two estrogen receptor (ER) subtypes (ERalpha and beta), two VTGs (VTG I and II), pregnane X receptor (PXR), and two cytochromes P450 (CYP) 3As (CYP3A38 and 3A40) in the livers of male medaka treated with AHTN and HHCB at 5, 50 and 500 microg/L. Quantitative real-time PCR analyses revealed that hepatic ERalpha, VTG I, VTG II, and CYP3A40 mRNA responded to 500 microg/L of AHTN and/or HHCB after 3 days exposure, whereas no effects of these compounds on ERbeta, PXR, and CYP3A38 mRNA transcription were observed. These results suggest that certain polycyclic musks, including AHTN and HHCB, induce the expression levels of hepatic ERalpha and VTG mRNA/protein and modulate expression levels of CYP3A40 mRNA in the livers of male medaka.
authors.affiliation: Faculty of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, 3-1-100 Tsukide, Kumamoto 862-8502, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yamauchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Masashi
authors.initials: M
authors.lastname: Hirano
authors.forename: Taiki
authors.initials: T
authors.lastname: Mori
authors.forename: Joon-Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Koji
authors.initials: K
authors.lastname: Arizono
mesh_terms: D000818:Animals; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D005260:Female; D029941:Fish Proteins / Q000235:genetics*; D005618:Fresh Water / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects*; D007814:Larva / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009990:Oryzias / Q000378:metabolism*; D011083:Polycyclic Compounds / Q000032:analysis / Q000633:toxicity*; D000077297:Pregnane X Receptor; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism; D014819:Vitellogenins / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000633:toxicity*
chemical_list: D029941:Fish Proteins; D011083:Polycyclic Compounds; D000077297:Pregnane X Receptor; D011960:Receptors, Estrogen; D011987:Receptors, Steroid; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D051544:Cytochrome P-450 CYP3A