PMID- 21296122
OWN - NLM
STAT- MEDLINE
DCOM- 20110506
LR  - 20131121
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 282
IP  - 3
DP  - 2011 Apr 11
TI  - Modulation of steroidogenic gene expression and hormone synthesis in H295R cells 
      exposed to PCP and TCP.
PG  - 146-53
LID - 10.1016/j.tox.2011.01.024 [doi]
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, 3.4muM) of PCP and TCP for 48h, and expression of specific genes 
      involved in steroidogenesis, including cytochrome P450 (CYP11A, CYP17, CYP19), 
      3betaHSD2, 17betaHSD4 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 17beta-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.
CI  - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved.
FAU - Ma, Yanbo
AU  - Ma Y
AD  - State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of 
      Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
FAU - Liu, Chunsheng
AU  - Liu C
FAU - Lam, Paul K S
AU  - Lam PK
FAU - Wu, Rudolf S S
AU  - Wu RS
FAU - Giesy, John P
AU  - Giesy JP
FAU - Hecker, Markus
AU  - Hecker M
FAU - Zhang, Xiaowei
AU  - Zhang X
FAU - Zhou, Bingsheng
AU  - Zhou B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110204
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Chlorophenols)
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Gonadal Steroid Hormones)
RN  - 0 (Phosphoproteins)
RN  - 0 (steroidogenic acute regulatory protein)
RN  - 3XMK78S47O (Testosterone)
RN  - 4TI98Z838E (Estradiol)
RN  - D9BSU0SE4T (Pentachlorophenol)
RN  - E0399OZS9N (Cyclic AMP)
RN  - MHS8C5BAUZ (2,4,6-trichlorophenol)
SB  - IM
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Chlorophenols/*toxicity
MH  - Cyclic AMP/metabolism
MH  - Endocrine Disruptors/*toxicity
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Estradiol/biosynthesis
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation/*drug effects
MH  - Gonadal Steroid Hormones/*biosynthesis/genetics
MH  - Humans
MH  - Pentachlorophenol/*toxicity
MH  - Phosphoproteins/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Testosterone/biosynthesis
EDAT- 2011/02/08 06:00
MHDA- 2011/05/07 06:00
CRDT- 2011/02/08 06:00
PHST- 2010/09/23 00:00 [received]
PHST- 2011/01/13 00:00 [revised]
PHST- 2011/01/31 00:00 [accepted]
PHST- 2011/02/08 06:00 [entrez]
PHST- 2011/02/08 06:00 [pubmed]
PHST- 2011/05/07 06:00 [medline]
AID - S0300-483X(11)00043-6 [pii]
AID - 10.1016/j.tox.2011.01.024 [doi]
PST - ppublish
SO  - Toxicology. 2011 Apr 11;282(3):146-53. doi: 10.1016/j.tox.2011.01.024. Epub 2011 
      Feb 4.