title: Effects of PCBs and MeSO2-PCBs on adrenocortical steroidogenesis in H295R human adrenocortical carcinoma cells.
abstract: Some endocrine disrupting chemicals (EDCs) in the environment have been shown to exert their biological effects through interference with steroidogenesis. In this study, the potential effects of four selected polychlorinated biphenyl (PCB) congeners (PCB101, PCB110, PCB126 and PCB149) as well as several of their environmentally-relevant methylsulfonyl-(MeSO(2)-) PCB metabolites (3'-MeSO(2)-CB101, 4'-MeSO(2)-CB101, 4'-MeSO(2)-CB110, 3'-MeSO(2)-CB149 and 4'-MeSO(2)-CB149) on adrenocortical steroidogenesis were evaluated by in vitro bioassay based on the human adrenocortical carcinoma H295R cell line. The PCBs included in the study represented different structures and potential mechanisms of action. Cells were exposed for 48 h to 10 microM of each PCB congener in the presence or absence of 20% (w/w) of their corresponding MeSO(2)-PCB metabolite(s). After the chemical treatments, changes in mRNA expression of 11 steroidogenic genes (CYP11A, CYP11B1, CYP11B2, CYP17, CYP19, CYP21, 3beta-HSD1, 3beta-HSD2, 17beta-HSD1, StAR and HMGR) were quantified using molecular beacon-based real-time RT-PCR. Genes coding for enzymes involved in the later or final steps of steroid production (CYP11B1, CYP11B2, CYP19, 3beta-HSD1, 3beta-HSD2 and 17beta-HSD1) were up-regulated to various extents by most PCBs. The greatest transcriptional activations (2.8-29.9-fold) were elicited by PCB110 on CYP11B1, CYP11B2, 3beta-HSD2 and CYP19, and PCB149 on CYP11B1, 3beta-HSD1 and 17beta-HSD1. Increased expression of these steroidogenic genes might ultimately lead to a change in hormonal balance through excessive production of steroid hormones including aldosterone, cortisol and estradiol. In addition, co-treatment with 3'- and 4'-MeSO(2)-PCB149 resulted in a significant decrease in PCB149-induced 3beta-HSD1 and 17beta-HSD1 expression. This result indicates that some PCB congeners and their MeSO(2)-metabolites may affect steroidogenesis via different mechanisms. Overall, these findings suggest that PCBs and PCB metabolites can affect regulation of adrenocortical steroidogenesis.
authors.affiliation: Department of Biology and Chemistry, Centre for Coastal Pollution and Conservation, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Richard M K
authors.initials: RM
authors.lastname: Yu
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.forename: Margaret B
authors.initials: MB
authors.lastname: Murphy
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.forename: Michael H W
authors.initials: MH
authors.lastname: Lam
authors.forename: Paul K S
authors.initials: PK
authors.lastname: Lam
authors.forename: Rudolf S S
authors.initials: RS
authors.lastname: Wu
authors.forename: Hongxia
authors.initials: H
authors.lastname: Yu
mesh_terms: D018268:Adrenocortical Carcinoma / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000187:drug effects* / Q000235:genetics; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D013256:Steroids / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
chemical_list: D013256:Steroids; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D006913:Hydroxysteroid Dehydrogenases