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Comparison of different androgen bioassays in the screening for environmental (anti)androgenic activity
Author(s) -
Christiaens Valerie,
Berckmans Pascale,
Haelens Annemie,
Witters Hilda,
Claessens Frank
Publication year - 2005
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1897/05-126r.1
Subject(s) - bioassay , androgen receptor , transactivation , androgen , biology , potency , ec50 , reporter gene , ligand binding assay , endocrine system , chemistry , pharmacology , receptor , endocrinology , biochemistry , in vitro , transcription factor , hormone , gene expression , gene , genetics , prostate cancer , cancer
Endocrine disruptors pose a growing threat to human and wildlife health. Validated test systems are required to study the mechanisms by which chemicals may interfere with the endocrine system. In order to identify compounds with (anti)androgenic activity, we used several in vitro bioassays, based on different androgen receptor (AR) functions, including AR transactivation and interaction between the amino‐terminal domain and the ligand‐binding domain. The AR activity assay, based on activation of the transcription of an androgen‐responsive reporter gene in the presence of androgen, proved to excel in terms of high fold induction range and low minimal detection limit. The EC50 value, defined as the concentration that leads to half the maximal response and reflecting the potency of the synthetic androgen R1881 (methyltrienolone), was found to be 250 pM, consistent with the high affinity of this ligand to the human AR. A number of environmental samples were tested in the bioassay. The bioassay also could be used to detect antiandrogenic activity, because known AR‐antagonists were able to inhibit R1881‐mediated transactivation.