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

Yanbo MA, Chunsheng LIU, Paul K. S. LAM, Shiu Sun Rudolf WU, John P. GIESY, Markus HECKER, Xiaowei ZHANG, Bingsheng ZHOU

Research output: Contribution to journalArticlespeer-review

27 Citations (Scopus)

Abstract

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. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)146-153
JournalToxicology
Volume282
Issue number3
DOIs
Publication statusPublished - 11 Apr 2011

Citation

Ma, Y., Liu, C., Lam, P. K. S., Wu, R. S. S., Giesy, J. P., Hecker, M., . . . Zhou, B. (2011). Modulation of steroidogenic gene expression and hormone synthesis in H295R cells exposed to PCP and TCP. Toxicology, 282(3), 146-153. doi: 10.1016/j.tox.2011.01.024

Keywords

  • Chlorophenol
  • Endocrine-disruption
  • Gene expression
  • Steroid hormone
  • cAMP
  • H295R

Fingerprint Dive into the research topics of 'Modulation of steroidogenic gene expression and hormone synthesis in H295R cells exposed to PCP and TCP'. Together they form a unique fingerprint.