Article: Modulation of steroidogenic gene expression and hormone synthesis in H295R cells exposed to PCP and TCP

File Download Links for fulltext
(May Require Subscription)
Supplementary

  • Basic View
  • Metadata View
  • XML View
TitleModulation of steroidogenic gene expression and hormone synthesis in H295R cells exposed to PCP and TCP
AuthorsMa, Y1 7
Liu, C7
Lam, PKS6
Wu, RSS4
Giesy, JP2 3 4 5 6
Hecker, M2
Zhang, X2
Zhou, B7
KeywordsCAMP
Chlorophenol
Endocrine-disruption
Gene expression
H295R
Steroid hormone
Issue Date2011
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/toxicol
CitationToxicology, 2011, v. 282 n. 3, p. 146-153 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.tox.2011.01.024
AbstractChlorophenols (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. © 2011 Elsevier Ireland Ltd.
ISSN0300-483X
2011 Impact Factor: 3.681
2011 SCImago Journal Rankings: 0.227
DOIhttp://dx.doi.org/10.1016/j.tox.2011.01.024
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorMa, Y
dc.contributor.authorLiu, C
dc.contributor.authorLam, PKS
dc.contributor.authorWu, RSS
dc.contributor.authorGiesy, JP
dc.contributor.authorHecker, M
dc.contributor.authorZhang, X
dc.contributor.authorZhou, B
dc.date.accessioned2012-09-20T08:25:46Z
dc.date.available2012-09-20T08:25:46Z
dc.date.issued2011
dc.description.abstractChlorophenols (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. © 2011 Elsevier Ireland Ltd.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationToxicology, 2011, v. 282 n. 3, p. 146-153 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.tox.2011.01.024
dc.identifier.citeulike8795310
dc.identifier.doihttp://dx.doi.org/10.1016/j.tox.2011.01.024
dc.identifier.epage153
dc.identifier.hkuros208998
dc.identifier.issn0300-483X
2011 Impact Factor: 3.681
2011 SCImago Journal Rankings: 0.227
dc.identifier.issue3
dc.identifier.pmid21296122
dc.identifier.scopuseid_2-s2.0-79952310970
dc.identifier.spage146
dc.identifier.urihttp://hdl.handle.net/10722/165950
dc.identifier.volume282
dc.languageeng
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/toxicol
dc.publisher.placeIreland
dc.relation.ispartofToxicology
dc.relation.referencesReferences in Scopus
dc.subject.meshChlorophenols - toxicity
dc.subject.meshEndocrine Disruptors - toxicity
dc.subject.meshGene Expression Regulation - drug effects
dc.subject.meshGonadal Steroid Hormones - biosynthesis - genetics
dc.subject.meshPentachlorophenol - toxicity
dc.subjectCAMP
dc.subjectChlorophenol
dc.subjectEndocrine-disruption
dc.subjectGene expression
dc.subjectH295R
dc.subjectSteroid hormone
dc.titleModulation of steroidogenic gene expression and hormone synthesis in H295R cells exposed to PCP and TCP
dc.typeArticle
Author Affiliations
  1. Graduate University of Chinese Academy of Sciences
  2. University of Saskatchewan
  3. King Saud University College of Science
  4. The University of Hong Kong
  5. Michigan State University
  6. City University of Hong Kong
  7. Institute of Hydrobiology, Chinese Academy of Sciences