Perfluorinated iodine alkalies (PFIs) are used widely in the organic fluorine industry. Increased production of PFIs has caused environmental health concern. 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, 17 beta-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 3 beta HSD2, 17 beta HSD; 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 17 beta-estradiol were elevated significantly, and the level of testosterone generation decreased upon treatment with 100 mu M 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 mu M 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 roup 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.
1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan, Peoples R China 2.Chinese Acad Sci, Ecoenvironm Sci Res Ctr, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China