T-Screen as a tool to identify thyroid hormone receptor active compounds
Gutleb, AC; Meerts, IATM; Bergsma, JH; Schriks, M; Murk, AJ
HERO ID
652770
Reference Type
Journal Article
Year
2005
Language
English
PMID
| HERO ID | 652770 |
|---|---|
| In Press | No |
| Year | 2005 |
| Title | T-Screen as a tool to identify thyroid hormone receptor active compounds |
| Authors | Gutleb, AC; Meerts, IATM; Bergsma, JH; Schriks, M; Murk, AJ |
| Journal | Environmental Toxicology and Pharmacology |
| Volume | 19 |
| Issue | 2 |
| Page Numbers | 231-238 |
| Abstract | The T-Screen represents an in vitro bioassay based on thyroid hormone dependent cell proliferation of a rat pituitary tumor cell line (GH3) in serum-free medium. It can be used to study interference of compds. with thyroid hormone at the cellular level, thus bridging the gap between limitations of assays using either isolated mols. (enzymes, transport proteins) or complex in vivo expts. with all the complex feedback mechanisms present. Compds. are tested both in the absence and presence of thyroid hormone (EC50 concn. of T3) to test for both agonistic and antagonistic potency. Thyroid hormones (3,3'-5-triiodothyronine: T3 and 3,3',5,5'-tetraiodothyroxine: T4) and compds. resembling the structure of thyroid hormones (3,3'-5-triiodothyroacetic acid: Triac; 3,3',5,5'-tetraiodothyroacetic acid: Tetrac) induced cell growth, with the rank order Triac > T3 > Tetrac > T4 (relative potency = 1.35>1 > 0.29>0.07), which is identical to published affinities of these compds. for nuclear thyroid hormone receptors. Exposure to 5,5'-diphenylhydantoin (DPH) in the presence of 0.25 nM T3 resulted in up to 60% decreased cell growth at 200 ?M DPH. No effect of DPH on basal metabolic activity of GH3 cells was obsd. at this concn. Fentinchloride (IC50 = 21 nM) decreased cell growth induced by 0.25 nM T3, whereas parallel exposure to these concns. in the absence of T3 did not alter basal metabolic activities of GH3 cells. Apolar sediment exts. from the Dommel (34%) and Terneuzen (14%) decreased cell growth in the presence of 0.25 nM T3, whereas the ext. from Hoogeveen increased cell growth (26%) and the ext. from North Sea Channel had no effect. The T-Screen proved to be a fast and functional assay for assessing thyroid hormone receptor active potencies of pure chems. or environmental mixts. |
| Doi | 10.1016/j.etap.2004.06.003 |
| Pmid | 21783481 |
| Wosid | WOS:000226642800005 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | thyroid hormone disruptor; EDC; bioassay; in vitro |