ToxSci Advance Access published online on June 8, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh191
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Zoology, National Food Safety and Toxicology Center, Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824
* To whom correspondence should be addressed. E-mail: jonespa7{at}msu.edu.
The potential for a variety of environmental contaminants to disturb endocrine function in wildlife and humans has been of recent concern. While much current effort is focused on the assessment of effects mediated through steroid hormone receptor-based mechanisms, there are potentially a variety of other mechanisms that could lead to "endocrine disruption". Recent studies have demonstrated that a variety of xenobiotics can alter the gene expression or activity of enzymes involved in steroidogenesis. By altering the production or catalytic activity of steroidogenic or steroid catabolizing enzymes, these chemicals have the potential to alter the steroid balance in organisms. To assess the potential of chemicals to alter steroidogenesis, an assay system was developed using a human adrenocortical carcinoma cell line, the H295R cell line, that retains the ability to synthesize most of the important steroidogenic enzymes. Methods were developed, optimized and validated to measure the expression of 10 genes involved in steroidogenesis by use of Real Time Quantitative Reverse Transcriptase PCR. The effects of several "model" chemicals known to alter steroid metabolism, both inducers and inhibitors, were assessed. Similar expression patterns were observed for chemicals acting through common mechanisms of action. Time-course studies demonstrated distinct time-dependent expression profiles for chemicals able to modulate steroid metabolism. The assay, which allows simultaneous analysis of the expression of numerous steroidogenic enzymes, would be useful as a sensitive and integrative screen for the many effects of chemicals on steroidogenesis.
Accepted May 27, 2004
Endocrine Toxicology
Assessment of the Effects of Chemicals on Expression of Ten Steroidogenic Genes in the H295R Cell Line Using Real Time PCR
2 ENTRIX Inc., 2295 Okemos Rd., East Lansing, MI 48864, USA
3 Department of Zoology, National Food Safety and Toxicology Center, Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824; City University of Hong Kong, Tat Chee Ave, Kowloon, Hong Kong, SAR China
4 Institute for Risk Assessment Sciences (IRAS), University of Utrecht, 3508 TD Utrecht, The Netherlands
5 City University of Hong Kong, Tat Chee Ave, Kowloon, Hong Kong, SAR China
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Z. Zhang and J. Hu Development and Validation of Endogenous Reference Genes for Expression Profiling of Medaka (Oryzias latipes) Exposed to Endocrine Disrupting Chemicals by Quantitative Real-Time RT-PCR Toxicol. Sci., February 1, 2007; 95(2): 356 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Sanderson The Steroid Hormone Biosynthesis Pathway as a Target for Endocrine-Disrupting Chemicals Toxicol. Sci., November 1, 2006; 94(1): 3 - 21. [Abstract] [Full Text] [PDF]
|
|