title: Effects of clofibric acid alone and in combination with 17β-estradiol on mRNA abundance in primary hepatocytes isolated from rainbow trout.
abstract: Clofibric acid (CA) is the active substance of lipid lowering drugs. It is resistant to degradation, polar in nature, and has been found ubiquitously in the aquatic environment. Though CA is classified as a peroxisomal proliferator in rodents and is considered as a potential endocrine disruptor, little information exists on the effects of CA in aquatic organisms, such as fish. In the present study, we examined the mRNA levels of peroxisome proliferator- and estrogen-sensitive genes on the exposure of primary rainbow trout (Oncorhynchus mykiss) hepatocytes to CA alone and in combination with the natural female sex hormone, 17β-estradiol (E2). Our results demonstrate that rainbow trout hepatocytes are relatively refractory to the effects of CA on the PPAR signaling pathway and lipid metabolism. Moreover, CA did not show recognizable estrogenic activity, but after the induction of vitellogenesis by E2, CA significantly reduced vitellogenin (VTG) mRNA abundance. Apparently, the indirect repression of VTG transcription, independent of estrogen receptors, occurred. The mechanism is not yet clearly understood but may involve disruption of the stabilization of VTG mRNA known to be induced by E2.
authors.affiliation: Department of Cell Toxicology, UFZ - Centre for Environmental Research, Permoserstraße 15, D-04318 Leipzig, Germany(1); RECETOX - Research Centre for Toxic Compounds in the Environment, Faculty of Science, Masaryk University, Kamenice 753/5, pavilion A29, CZ-62500 Brno, Czech Republic. Electronic address: sovadinova@recetox.muni.cz.
authors.forename: I
authors.initials: I
authors.lastname: Sovadinová
authors.affiliation: Department of Cell Toxicology, UFZ - Centre for Environmental Research, Permoserstraße 15, D-04318 Leipzig, Germany(1); Harlan Laboratories Ltd., Zelgliweg 1, CH-4452 Itingen, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Liedtke
authors.affiliation: Department of Cell Toxicology, UFZ - Centre for Environmental Research, Permoserstraße 15, D-04318 Leipzig, Germany(1); Department of Environmental Toxicology, Eawag, Swiss Federal Institute of Aquatic Science and Technology, Überlandstrasse 133, P.O. Box 611, CH-8600 Duebendorf, Switzerland; School of Architecture, Civil and Environmental Engineering (ENAC), EPF Lausanne, GC A2 392 (Building GC), Station 18, CH-1015 Lausanne, Switzerland; Department of Environmental Systems Science, Institute of Biogeochemistry and Pollutant Dynamics, ETH Zürich, Universitätstrasse 16, CH-8092 Zürich, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Schirmer
mesh_terms: D000818:Animals; D053304:Apolipoprotein C-II / Q000235:genetics; D002478:Cells, Cultured; D002995:Clofibric Acid / Q000633:toxicity*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004958:Estradiol / Q000633:toxicity*; D020847:Estrogen Receptor Modulators / Q000633:toxicity*; D005260:Female; D029941:Fish Proteins / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000633:toxicity; D017686:Oncorhynchus mykiss; D012333:RNA, Messenger / Q000378:metabolism; D014819:Vitellogenins / Q000235:genetics; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D053304:Apolipoprotein C-II; D020847:Estrogen Receptor Modulators; D029941:Fish Proteins; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D004958:Estradiol; D002995:Clofibric Acid; D003577:Cytochrome P-450 Enzyme System; C112263:CYP2M1 protein, Oncorhynchus mykiss; D051544:Cytochrome P-450 CYP3A; D005982:Glutathione Transferase
keywords: Clofibric acid; Endocrine disruption; Primary fish hepatocytes; Rainbow trout; Vitellogenin