[Ma, Yanbo; Liu, Chunsheng; Zhou, Bingsheng] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China; [Ma, Yanbo] Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China; [Lam, Paul K. S.; Giesy, John P.] City Univ Hong Kong, Dept Biol & Chem, Kowloon, Hong Kong, Peoples R China; [Wu, Rudolf S. S.; Giesy, John P.] Univ Hong Kong, Sch Biol Sci, Hong Kong, Hong Kong, Peoples R China; [Giesy, John P.] Univ Saskatchewan, Dept Vet, Saskatoon, SK, Canada; [Hecker, Markus; Zhang, Xiaowei] Univ Saskatchewan, Toxicol Ctr, Saskatoon, SK, Canada; [Giesy, John P.] King Saud Univ, Dept Zool, Coll Sci, Riyadh 11451, Saudi Arabia; [Giesy, John P.] Michigan State Univ, Dept Zool, E Lansing, MI 48824 USA; [Giesy, John P.] Michigan State Univ, Ctr Integrat Toxicol, E Lansing, MI 48824 USA
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.
Ma, Yanbo; Liu, Chunsheng; Lam, Paul K. S.; Wu, Rudolf S. S.; Giesy, John P.; Hecker, Markus; Zhang, Xiaowei; Zhou, Bingsheng.Modulation of steroidogenic gene expression and hormone synthesis in H295R cells exposed to PCP and TCP,TOXICOLOGY,2011,282(3):146-153