TY - JOUR
T1 - Modulation of steroidogenic gene expression and hormone synthesis in H295R cells exposed to PCP and TCP
AU - Ma, Yanbo
AU - Liu, Chunsheng
AU - Lam, Paul K.S.
AU - Wu, Rudolf S.S.
AU - Giesy, John P.
AU - Hecker, Markus
AU - Zhang, Xiaowei
AU - Zhou, Bingsheng
N1 - Funding Information:
This work was supported by C hinese Academy of Sciences ( KZCX2-YW-Q02-05 ), the NSFC of China ( 20890113 ), the FEBL project ( 2008FBZ10 ) and a Discovery Grant from the NSERC of Canada ( 326415-07 ), and a grant from the Western Economic Diversification Canada ( 6578 and 6807 ). Prof. Giesy was supported by the Canada Research Chair program and an at-large Chair Professorship at the Department of Biology and Chemistry and State Key Laboratory in Marine Pollution, City University of Hong Kong.
PY - 2011/4/11
Y1 - 2011/4/11
N2 - Chlorophenols (CPs) have been suspected to disrupt the endocrine system and thus affect human and wildlife reproduction but less is known about the underlying mechanism. In this study, we investigated the effects of pentachlorophenol (PCP) and 2,4,6-trichlorophenol (TCP) on human adrenocortical carcinoma cell line (H295R). The H295R cells were exposed to environmentally relevant concentration (0.0, 0.4, 1.1, 3.4 μM) of PCP and TCP for 48. h, and expression of specific genes involved in steroidogenesis, including cytochrome P450 (CYP11A, CYP17, CYP19), 3βHSD2, 17βHSD4 and StAR was quantitatively measured using real-time polymerase chain reaction. The selected gene expressions were significantly down-regulated compared with those in the control group. Exposure to PCP and TCP significantly decreased production of both testosterone (T) and 17β-estradiol (E2). Furthermore, a dose-dependent decrease of cellular cAMP was observed in H295R cells exposed to both PCP and TCP. A time-course study revealed that the observed selected steroidogenic gene expressions and protein abundance (StAR) are consistent with reduced cellular cAMP concentrations. The results showed that PCP and TCP may inhibit steroidogenesis by disrupting cAMP signaling. The research indicates that H295R cells can be used as an in vitro model for endocrine disruption assay for chlorophenols and the mechanism involvement of disturbing cAMP signaling.
AB - Chlorophenols (CPs) have been suspected to disrupt the endocrine system and thus affect human and wildlife reproduction but less is known about the underlying mechanism. In this study, we investigated the effects of pentachlorophenol (PCP) and 2,4,6-trichlorophenol (TCP) on human adrenocortical carcinoma cell line (H295R). The H295R cells were exposed to environmentally relevant concentration (0.0, 0.4, 1.1, 3.4 μM) of PCP and TCP for 48. h, and expression of specific genes involved in steroidogenesis, including cytochrome P450 (CYP11A, CYP17, CYP19), 3βHSD2, 17βHSD4 and StAR was quantitatively measured using real-time polymerase chain reaction. The selected gene expressions were significantly down-regulated compared with those in the control group. Exposure to PCP and TCP significantly decreased production of both testosterone (T) and 17β-estradiol (E2). Furthermore, a dose-dependent decrease of cellular cAMP was observed in H295R cells exposed to both PCP and TCP. A time-course study revealed that the observed selected steroidogenic gene expressions and protein abundance (StAR) are consistent with reduced cellular cAMP concentrations. The results showed that PCP and TCP may inhibit steroidogenesis by disrupting cAMP signaling. The research indicates that H295R cells can be used as an in vitro model for endocrine disruption assay for chlorophenols and the mechanism involvement of disturbing cAMP signaling.
KW - CAMP
KW - Chlorophenol
KW - Endocrine-disruption
KW - Gene expression
KW - H295R
KW - Steroid hormone
UR - https://www.scopus.com/pages/publications/79952310970
U2 - 10.1016/j.tox.2011.01.024
DO - 10.1016/j.tox.2011.01.024
M3 - Article
C2 - 21296122
AN - SCOPUS:79952310970
SN - 0300-483X
VL - 282
SP - 146
EP - 153
JO - Toxicology
JF - Toxicology
IS - 3
ER -