TY - JOUR
T1 - Effects of PCBs and MeSO2-PCBs on adrenocortical steroidogenesis in H295R human adrenocortical carcinoma cells
AU - Xu, Yan
AU - Yu, Richard M.K.
AU - Zhang, Xiaowei
AU - Murphy, Margaret B.
AU - Giesy, John P.
AU - Lam, Michael H.W.
AU - Lam, Paul K.S.
AU - Wu, Rudolf S.S.
AU - Yu, Hongxia
N1 - Funding Information:
The authors would like to thank Dr. Robert J. Letcher for his critical review of the manuscript. The work described in this paper was supported by a Central Allocation Grant (Project No. 8730011) from the Research Grants Council of Hong Kong and a research grant (Project No. 7001539) from City University of Hong Kong.
PY - 2006/5
Y1 - 2006/5
N2 - 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-(MeSO2-) PCB metabolites (3′-MeSO2-CB101, 4′-MeSO2-CB101, 4′-MeSO2-CB110, 3′-MeSO2-CB149 and 4′-MeSO2-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 μM of each PCB congener in the presence or absence of 20% (w/w) of their corresponding MeSO2-PCB metabolite(s). After the chemical treatments, changes in mRNA expression of 11 steroidogenic genes (CYP11A, CYP11B1, CYP11B2, CYP17, CYP19, CYP21, 3β-HSD1, 3β-HSD2, 17β-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, 3β-HSD1, 3β-HSD2 and 17β-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, 3β-HSD2 and CYP19, and PCB149 on CYP11B1, 3β-HSD1 and 17β-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′-MeSO2-PCB149 resulted in a significant decrease in PCB149-induced 3β-HSD1 and 17β-HSD1 expression. This result indicates that some PCB congeners and their MeSO2-metabolites may affect steroidogenesis via different mechanisms. Overall, these findings suggest that PCBs and PCB metabolites can affect regulation of adrenocortical steroidogenesis.
AB - 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-(MeSO2-) PCB metabolites (3′-MeSO2-CB101, 4′-MeSO2-CB101, 4′-MeSO2-CB110, 3′-MeSO2-CB149 and 4′-MeSO2-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 μM of each PCB congener in the presence or absence of 20% (w/w) of their corresponding MeSO2-PCB metabolite(s). After the chemical treatments, changes in mRNA expression of 11 steroidogenic genes (CYP11A, CYP11B1, CYP11B2, CYP17, CYP19, CYP21, 3β-HSD1, 3β-HSD2, 17β-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, 3β-HSD1, 3β-HSD2 and 17β-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, 3β-HSD2 and CYP19, and PCB149 on CYP11B1, 3β-HSD1 and 17β-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′-MeSO2-PCB149 resulted in a significant decrease in PCB149-induced 3β-HSD1 and 17β-HSD1 expression. This result indicates that some PCB congeners and their MeSO2-metabolites may affect steroidogenesis via different mechanisms. Overall, these findings suggest that PCBs and PCB metabolites can affect regulation of adrenocortical steroidogenesis.
KW - H295R
KW - MeSO-PCBs
KW - Polychlorinated biphenyls
KW - Steroidogenesis
UR - http://www.scopus.com/inward/record.url?scp=33646066554&partnerID=8YFLogxK
U2 - 10.1016/j.chemosphere.2005.08.013
DO - 10.1016/j.chemosphere.2005.08.013
M3 - Article
C2 - 16216300
AN - SCOPUS:33646066554
SN - 0045-6535
VL - 63
SP - 772
EP - 784
JO - Chemosphere
JF - Chemosphere
IS - 5
ER -
