Effects of fifteen PBDE metabolites, DE71, DE79 and TBBPA on steroidogenesis in the H295R cell line.
Polybrominated diphenyl ethers (PBDEs) and tetrabromobisphenol A (TBBPA) are brominated flame retardants that are produced in large quantities and are commonly used in construction materials, textiles, and as polymers in electronic equipment. Environmental and human levels of PBDEs have been increasing in the past 30 years, but the toxicity of PBDEs is not fully understood. Studies on their effects are relatively limited, and show that PBDEs are neurotoxins and potential endocrine disrupters. Hydroxylated (OH) and methoxylated (MeO) PBDEs have also been reported in the adipose tissue, blood and milk of wild animals and humans. In the present study, 15 PBDE metabolites, two BDE mixtures (DE71 and DE79), and TBBPA were studied individually to determine their effects on ten steroidogenic genes, aromatase activity, and concentrations of two steroid hormones (testosterone and 17beta-estradiol) in the H295R human adrenocortical carcinoma cell line. Exposure to 0.05 microM 2'-OH-BDE-68 significantly induced the expression of CYP11A, CYP11B2, CYP17, CYP21, 3betaHSD2, 17betaHSD1, and 17betaHSD4, and the expression of StAR was induced by 6-OH-BDE-90 at the three exposure concentrations. Exposure to DE71 and DE79 resulted in dose-dependent trend towards induction, but these effects were not significant. Exposure to 0.5 microM 2-OH-BDE-123 and 2-MeO-BDE-123 resulted in significantly greater aromatase activity. However, none of the compounds affected sex hormone production at the concentrations tested. Generally, OH-BDEs had a much stronger ability to affect steroidogenic gene expression than MeO-BDEs.
Song
Renfang
R
Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong.
He
Yuhe
Y
Murphy
Margaret B
MB
Yeung
Leo W Y
LW
Yu
Richard M K
RM
Lam
Michael H W
MH
Lam
Paul K S
PK
Hecker
Markus
M
Giesy
John P
JP
Wu
Rudolf S S
RS
Zhang
Wenbing
W
Sheng
Guoying
G
Fu
Jiamo
J
D001141:Aromatase / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004958:Estradiol / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics; D010647:Phenyl Ethers / Q000633:toxicity*; D010750:Phosphoproteins / Q000235:genetics; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D013739:Testosterone / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
D010647:Phenyl Ethers; D010750:Phosphoproteins; D011075:Polybrominated Biphenyls; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; D006913:Hydroxysteroid Dehydrogenases; D001141:Aromatase