The H295R system for evaluation of endocrine-disrupting effects.
The present studies were undertaken to evaluate the utility of the H295R system as an in vitro assay to assess the potential of chemicals to modulate steroidogenesis. The effects of four model chemicals on the expression of ten steroidogenic genes and on the production of three steroid hormones were examined. Exposures with individual model chemicals as well as binary mixtures were conducted. Although the responses reflect the known mode of action of the various compounds, the results show that designating a chemical as "specific inducer or inhibitor" is unwise. Not all changes in the mixture exposures could be predicted based on results from individual chemical exposures. Hormone production was not always directly related to gene expression. The H295R system integrates the effects of direct-acting hormone agonists and antagonists as well as chemicals affecting signal transduction pathways for steroid production and provides data on both gene expression and hormone secretion which makes this cell line a valuable tool to examine effects of chemicals on steroidogenesis.
Gracia
Tannia
T
Department of Zoology, 218C National Food Safety and Toxicology Center, Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824-1311, USA. gracia@msu.edu
Hilscherova
Klara
K
Jones
Paul D
PD
Newsted
John L
JL
Zhang
Xiaowei
X
Hecker
Markus
M
Higley
Eric B
EB
Sanderson
J T
JT
Yu
Richard M K
RM
Wu
Rudolf S S
RS
Giesy
John P
JP
D000616:Aminoglutethimide / Q000494:pharmacology; D001681:Biological Assay; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D004347:Drug Interactions; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007654:Ketoconazole / Q000494:pharmacology; D008797:Metyrapone / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*
D052244:Endocrine Disruptors; D000616:Aminoglutethimide; D005576:Colforsin; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D007654:Ketoconazole; D008797:Metyrapone