کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2603358 1133817 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Establishment of yeast reporter assay systems to detect ligands of thyroid hormone receptors α and β
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Establishment of yeast reporter assay systems to detect ligands of thyroid hormone receptors α and β
چکیده انگلیسی

Thyroid hormones are essential for proper development and differentiation in vertebrates. Recently, concern over the disruption of thyroid hormone homeostasis by industrial chemicals and environmental pollutants has been spreading. To evaluate these chemicals, several bioassays have been developed to detect thyroid hormone ligand activity. Nevertheless, a simple and useful assay is required for the assessment of an enormous number of environmental chemicals. We established yeast reporter assays by expression of full-length thyroid hormone receptor (TRα or TRβ) cDNA and of the TR-dependent reporter gene in yeasts. By additional introduction of the general coactivator SRC-1 cDNA into the yeasts, a higher response to endogenous thyroid hormones, thyroxine (T4), and triiodothyronine (T3) was obtained. The EC50 values for T3 were 35 and 1.5 nM for TRα and TRβ assay yeasts, respectively. We tested four chemicals, tetrabromobisphenol A, tetramethylbisphenol A, 2-isopropylphenol, and o-t-butylphenol, which are suspected to have thyroid hormone-disrupting activity. All four chemicals showed agonistic activities in both assay yeasts; however, their activities were weak in comparison with endogenous TR ligands. Antagonist activities of 2-isopropylphenol and o-t-butylphenol were also found in the TRα yeast assay. Taken together, these assay yeasts will be powerful tools for assessing TR ligand activity of industrial chemicals and environmental pollutants.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 24, Issue 2, March 2010, Pages 638–644
نویسندگان
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