Modulation of steroidogenic gene expression and hormone synthesis in H295R cells exposed to PCP and TCP

CORC > 水生生物研究所 > 中科院水生所知识产出（2009年前） > 水环境工程研究中心 > 期刊论文

	Modulation of steroidogenic gene expression and hormone synthesis in H295R cells exposed to PCP and TCP
	Ma, Yanbo 1,2; Liu, Chunsheng 1; Lam, Paul K. S.3; Wu, Rudolf S. S.4; Giesy, John P.3,4,5,7,8,9; Hecker, Markus 6; Zhang, Xiaowei 6; Zhou, Bingsheng 1
刊名	TOXICOLOGY
	2011-04-11
卷号	282 期号:3 页码:146-153
关键词	Chlorophenol Endocrine-disruption Gene expression Steroid hormone cAMP H295R
ISSN号	0300-483X
通讯作者	Zhou, BS, Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China ; bszhou@ihb.ac.cn
中文摘要	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.
英文摘要	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.
学科主题	Pharmacology & Pharmacy; Toxicology
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Pharmacology & Pharmacy ; Toxicology
研究领域[WOS]	Pharmacology & Pharmacy ; Toxicology
关键词[WOS]	ADRENOCORTICAL CARCINOMA-CELLS ; AROMATASE CYP19 ACTIVITY ; BROMINATED FLAME RETARDANTS ; ACUTE REGULATORY PROTEIN ; IN-VITRO ; PBDE METABOLITES ; PRIMARY CULTURES ; WASTE-WATER ; PENTACHLOROPHENOL ; INHIBITION
收录类别	SCI
资助信息	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
语种	英语
WOS记录号	WOS:000289327500010
公开日期	2011-06-30
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/15646]
专题	水生生物研究所_水环境工程研究中心_期刊论文
作者单位	1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China 2.Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China 3.City Univ Hong Kong, Dept Biol & Chem, Kowloon, Hong Kong, Peoples R China 4.Univ Hong Kong, Sch Biol Sci, Hong Kong, Hong Kong, Peoples R China 5.Univ Saskatchewan, Dept Vet, Saskatoon, SK, Canada 6.Univ Saskatchewan, Toxicol Ctr, Saskatoon, SK, Canada 7.King Saud Univ, Dept Zool, Coll Sci, Riyadh 11451, Saudi Arabia 8.Michigan State Univ, Dept Zool, E Lansing, MI 48824 USA 9.Michigan State Univ, Ctr Integrat Toxicol, E Lansing, MI 48824 USA
推荐引用方式 GB/T 7714	Ma, Yanbo,Liu, Chunsheng,Lam, Paul K. S.,et al. Modulation of steroidogenic gene expression and hormone synthesis in H295R cells exposed to PCP and TCP[J]. TOXICOLOGY,2011,282(3):146-153.
APA	Ma, Yanbo.,Liu, Chunsheng.,Lam, Paul K. S..,Wu, Rudolf S. S..,Giesy, John P..,...&Zhou, Bingsheng.(2011).Modulation of steroidogenic gene expression and hormone synthesis in H295R cells exposed to PCP and TCP.TOXICOLOGY,282(3),146-153.
MLA	Ma, Yanbo,et al."Modulation of steroidogenic gene expression and hormone synthesis in H295R cells exposed to PCP and TCP".TOXICOLOGY 282.3(2011):146-153.