Perfluorooctyl Iodide Stimulates Steroidogenesis in H295R Cells via a Cyclic Adenosine Monophosphate Signaling Pathway.
Article Details
- CitationCopy to clipboard
Wang C, Ruan T, Liu J, He B, Zhou Q, Jiang G
Perfluorooctyl Iodide Stimulates Steroidogenesis in H295R Cells via a Cyclic Adenosine Monophosphate Signaling Pathway.
Chem Res Toxicol. 2015 May 18;28(5):848-54. doi: 10.1021/tx5004563. Epub 2015 Apr 28.
- PubMed ID
- 25871633 [ View in PubMed]
- 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, 17beta-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, 3betaHSD2, 17betaHSD, 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 17beta-estradiol were elevated significantly, and the level of testosterone generation decreased upon treatment with 100 muM 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 muM 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.
DrugBank Data that Cites this Article
- Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Colforsin Experimental Investigational CYP11A1 1583 upregulated Colforsin results in increased expression of CYP11A1 mRNA 15q24.1 Colforsin Experimental Investigational CYP11B1 1584 upregulated Colforsin results in increased expression of CYP11B1 mRNA 8q24.3 Colforsin Experimental Investigational CYP11B2 1585 upregulated Colforsin results in increased expression of CYP11B2 mRNA 8q24.3 Colforsin Experimental Investigational CYP17A1 1586 upregulated Colforsin results in increased expression of CYP17A1 mRNA 10q24.32 Colforsin Experimental Investigational CYP19A1 1588 upregulated Colforsin results in increased expression of CYP19A1 mRNA 15q21.2 Colforsin Experimental Investigational CYP21A2 1589 upregulated Colforsin results in increased expression of CYP21A2 mRNA 6p21.33 Colforsin Experimental Investigational HSD3B2 3284 upregulated Colforsin results in increased expression of HSD3B2 mRNA 1p12 Colforsin Experimental Investigational STAR 6770 upregulated Colforsin results in increased expression of STAR mRNA 8p11.23 Perflubron Investigational CYP11A1 1583 upregulated perflubron results in increased expression of CYP11A1 mRNA 15q24.1 Perflubron Investigational CYP11B1 1584 upregulated perflubron results in increased expression of CYP11B1 mRNA 8q24.3 Perflubron Investigational CYP11B2 1585 upregulated perflubron results in increased expression of CYP11B2 mRNA 8q24.3 Perflubron Investigational CYP17A1 1586 upregulated perflubron results in increased expression of CYP17A1 mRNA 10q24.32 Perflubron Investigational CYP19A1 1588 upregulated perflubron results in increased expression of CYP19A1 mRNA 15q21.2 Perflubron Investigational CYP21A2 1589 upregulated perflubron results in increased expression of CYP21A2 mRNA 6p21.33 Perflubron Investigational HMGCR 3156 upregulated perflubron results in increased expression of HMGCR mRNA 5q13.3 Perflubron Investigational HSD17B1 3292 upregulated perflubron results in increased expression of HSD17B1 mRNA 17q21.2 Perflubron Investigational HSD3B2 3284 upregulated perflubron results in increased expression of HSD3B2 mRNA 1p12 Perflubron Investigational STAR 6770 upregulated perflubron results in increased expression of STAR mRNA 8p11.23