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.

Department of Cell Toxicology UFZ Centre for Environmental Research Permoserstraße 15 D 04318 Leipzig Germany ; Harlan Laboratories Ltd Zelgliweg 1 CH 4452 Itingen Switzerland

Department of Cell Toxicology UFZ Centre for Environmental Research Permoserstraße 15 D 04318 Leipzig Germany ; RECETOX Research Centre for Toxic Compounds in the Environment Faculty of Science Masaryk University Kamenice 753 5 pavilion A29 CZ 62500 Brno Czech Republic

Department of Cell Toxicology UFZ Centre for Environmental Research Permoserstraße 15 D 04318 Leipzig Germany 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

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