title: Perfluorooctyl Iodide Stimulates Steroidogenesis in H295R Cells via a Cyclic Adenosine Monophosphate Signaling Pathway.
abstract: Perfluorinated iodine alkanes (PFIs) are used widely in the organic fluorine industry. Increased production of PFIs has caused environmental health concerns. To evaluate the potential endocrine-disrupting effect of PFIs, we investigated the effects of perfluorooctyl iodide (PFOI) on steroidogenesis in human adrenocortical carcinoma cells (H295R). Levels of aldosterone, cortisol, 17β-estradiol, and testosterone were measured in H295R culture medium upon treatment with perfluorooctanoic acid (PFOA) and PFIs. Expression of 10 steroidogenic genes (StAR, HMGR, CYP11A1, 3βHSD2, 17βHSD, CYP17, CYP21, CYP11B1, CYP11B2, and CYP19) was measured by real-time polymerase chain reaction. Levels of cyclic adenosine monophosphate (cAMP) and adenylate cyclase (AC) activity were measured to understand the underlying mechanism of steroidogenic perturbations. Levels of production of aldosterone, cortisol, and 17β-estradiol were elevated significantly, and the level of testosterone generation decreased upon treatment with 100 μM PFOI. Similar to the effect induced by forskolin (AC activator), expression of all 10 genes involved in the synthesis of steroid hormones was upregulated significantly upon exposure to 100 μM PFOI. PFOA had no effect on steroid hormone production or steroidogenic gene expression even though it is highly structurally similar with PFOI. Therefore, the terminal -CF2I group in PFOI could be a critical factor for mediation of steroidogenesis. PFOI increased AC activity and cAMP levels in H295R cells, which implied an underlying mechanism for the disturbance of steroidogenesis. These data suggest that PFOI may act as an AC activator, thereby stimulating steroidogenesis by activating a cAMP signaling pathway.
authors: †State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, People's Republic of China.|‡State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors: Chang
authors: C
authors: Wang
authors: ‡State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors: Ting
authors: T
authors: Ruan
authors: ‡State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors: Jiyan
authors: J
authors: Liu
authors: ‡State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors: Bin
authors: B
authors: He
authors: ‡State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors: Qunfang
authors: Q
authors: Zhou
authors: ‡State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors: Guibin
authors: G
authors: Jiang
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism; D045744:Cell Line, Tumor; D052244:Endocrine Disruptors / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism; D005466:Fluorocarbons / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006842:Hydrocarbons, Brominated; D006854:Hydrocortisone / Q000378:metabolism; D015398:Signal Transduction; D013256:Steroids / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D013256:Steroids; D013739:Testosterone; D000450:Aldosterone; D004958:Estradiol; D000244:Adenosine Diphosphate; C003072:perflubron; D006854:Hydrocortisone