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Effects of fluorotelomer alcohol 8/2 FTOH on steroidogenesis in H295R cells: Targeting the cAMP signalling cascade
Liu, Chunsheng; Zhang, Xiaowei; Chang, Hong; Jones, Paul; Wiseman, Steve; Naile, Jonathan; Hecker, Markus; Giesy, John P.; Zhou, Bingsheng; Zhang, XW, Nanjing Univ, Sch Environm, Nanjing 210089, Peoples R China
2010
Source PublicationTOXICOLOGY AND APPLIED PHARMACOLOGY
ISSN0041-008X
Volume247Issue:3Pages:222-228
AbstractPrevious studies have demonstrated that perfluorinated chemicals (PFCs) can affect reproduction by disruption of steroidogenesis in experimental animals. However, the underlying mechanism(s) of this disruption remain unknown. Here we investigated the effects and mechanisms of action of 1H, 1H, 2H, 2H-perfluoro-decan-1-ol (8:2 FTOH) on steroidogenesis using a human adrenocortical carcinoma cell line (H295R) as a model. H295R cells were exposed to 0, 7.4, 22.2 or 66.6 mu M 8:2 FTOH for 24 h and productions of progesterone, 17 alpha-OH-progesterone, androstenedione, testosterone, deoxycorticosterone, corticosterone and cortisol were quantified by HPLC-MS/MS. With the exception of progesterone, 8:2 FTOH treatment significantly decreased production of all hormones in the high dose group. Exposure to 8:2 FTOH significantly down-regulated cAMP-dependent mRNA expression and protein abundance of several key steroidogenic enzymes, including StAR, CYP11A, CYP11B1, CYP11B2, CYP17 and CYP21. Furthermore, a dose-dependent decrease of cellular cAMP levels was observed in H295R cells exposed to 8:2 FTOH. The observed responses are consistent with reduced cellular CAMP levels. Exposure to 8:2 FTOH resulted in significantly less basal (+GTP) and isoproterenol-stimulated adenylate cyclase activities, but affected neither total cellular ATP level nor basal (-GTP) or NaF-stimulated adenylate cyclase activities, suggesting that inhibition of steroidogenesis may be due to an alteration in membrane properties. Metabolites of 8:2 FTOH were not detected by HPLC-MS/MS, suggesting that 8:2 FTOH was not metabolized by H295R cells. Overall, the results show that 8:2 FTOH may inhibit steroidogenesis by disrupting the cAMP signalling cascade. (C) 2010 Elsevier Inc. All rights reserved.
KeywordSteroid Hormone Production Gene Expression Adenylate Cyclase Ftoh
Department[Zhang, Xiaowei; Giesy, John P.] Nanjing Univ, Sch Environm, Nanjing 210089, Peoples R China; [Zhang, Xiaowei; Giesy, John P.] Nanjing Univ, State Key Lab Pollut Control & Resource Reuse, Nanjing 210089, Peoples R China; [Liu, Chunsheng; Zhou, Bingsheng] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China; [Liu, Chunsheng] Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China; [Chang, Hong; Jones, Paul; Wiseman, Steve; Naile, Jonathan; Hecker, Markus; Giesy, John P.] Univ Saskatchewan, Biomed Sci & Toxicol Ctr, Dept Vet, Saskatoon, SK, Canada; [Hecker, Markus] ENTRIX Inc, Saskatoon, SK, Canada; [Giesy, John P.] City Univ Hong Kong, Dept Biol & Chem, Kowloon, Hong Kong, Peoples R China
Subject AreaPharmacology & Pharmacy ; Toxicology
Funding OrganizationNational Natural Science Foundation of China [20890113, 20877094]; NSERC of Canada [326415-07]; WED Canada [6578, 6807] ; National Natural Science Foundation of China [20890113, 20877094]; NSERC of Canada [326415-07]; WED Canada [6578, 6807] ; National Natural Science Foundation of China [20890113, 20877094]; NSERC of Canada [326415-07]; WED Canada [6578, 6807] ; National Natural Science Foundation of China [20890113, 20877094]; NSERC of Canada [326415-07]; WED Canada [6578, 6807]
Indexed BySCI
Language英语
WOS IDWOS:000281658300007
Funding OrganizationNational Natural Science Foundation of China [20890113, 20877094]; NSERC of Canada [326415-07]; WED Canada [6578, 6807] ; National Natural Science Foundation of China [20890113, 20877094]; NSERC of Canada [326415-07]; WED Canada [6578, 6807] ; National Natural Science Foundation of China [20890113, 20877094]; NSERC of Canada [326415-07]; WED Canada [6578, 6807] ; National Natural Science Foundation of China [20890113, 20877094]; NSERC of Canada [326415-07]; WED Canada [6578, 6807]
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Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/13685
Collection水环境工程研究中心_期刊论文
Corresponding AuthorZhang, XW, Nanjing Univ, Sch Environm, Nanjing 210089, Peoples R China
Recommended Citation
GB/T 7714
Liu, Chunsheng,Zhang, Xiaowei,Chang, Hong,et al. Effects of fluorotelomer alcohol 8/2 FTOH on steroidogenesis in H295R cells: Targeting the cAMP signalling cascade[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2010,247(3):222-228.
APA Liu, Chunsheng.,Zhang, Xiaowei.,Chang, Hong.,Jones, Paul.,Wiseman, Steve.,...&Zhang, XW, Nanjing Univ, Sch Environm, Nanjing 210089, Peoples R China.(2010).Effects of fluorotelomer alcohol 8/2 FTOH on steroidogenesis in H295R cells: Targeting the cAMP signalling cascade.TOXICOLOGY AND APPLIED PHARMACOLOGY,247(3),222-228.
MLA Liu, Chunsheng,et al."Effects of fluorotelomer alcohol 8/2 FTOH on steroidogenesis in H295R cells: Targeting the cAMP signalling cascade".TOXICOLOGY AND APPLIED PHARMACOLOGY 247.3(2010):222-228.
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