Journal
TOXICOLOGY
Volume 282, Issue 3, Pages 146-153Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2011.01.024
Keywords
Chlorophenol; Endocrine-disruption; Gene expression; Steroid hormone; cAMP; H295R
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Funding
- Chinese Academy of Sciences [KZCX2-YW-Q02-05]
- NSFC of China [20890113]
- NSERC of Canada [2008FBZ10, 326415-07]
- Western Economic Diversification Canada [6578, 6807]
- Canada Research Chair program
- Department of Biology and Chemistry and State Key Laboratory in Marine Pollution, City University of Hong Kong
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Chlorophenols (CPs) have been suspected to disrupt the endocrine system and thus affect human and wildlife reproduction but less is known about the underlying mechanism. In this study, we investigated the effects of pentachlorophenol (PCP) and 2.4,6-trichlorophenol (TCP) on human adrenocortical carcinoma cell line (H295R). The H295R cells were exposed to environmentally relevant concentration (0.0, 0.4, 1.1,3.4 mu M) of PCP and TCP for 48 h, and expression of specific genes involved in steroidogenesis, including cytochrome P450 (CYP11A,CYP17,CYP19),3 beta HSD2,17 beta HSD4 and StAR was quantitatively measured using real-time polymerase chain reaction. The selected gene expressions were significantly down-regulated compared with those in the control group. Exposure to PCP and TCP significantly decreased production of both testosterone (T) and 17 beta-estradiol (E2). Furthermore, a dose-dependent decrease of cellular cAMP was observed in H295R cells exposed to both PCP and TCP. A time-course study revealed that the observed selected steroidogenic gene expressions and protein abundance (StAR) are consistent with reduced cellular CAMP concentrations. The results showed that PCP and TCP may inhibit steroidogenesis by disrupting cAMP signaling. The research indicates that H295R cells can be used as an in vitro model for endocrine disruption assay for chlorophenols and the mechanism involvement of disturbing cAMP signaling. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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