Related Experiment Videos
Thyromimetic effect of peroxisome proliferators
R Hertz1, B Kalderon, J Bar-Tana
1Department of Human Nutrition and Metabolism, Hebrew University, Hadassah Medical School, Jerusalem, Israel.
Biochimie
|January 1, 1993
Summary
Peroxisome proliferators (PP) mimic thyroid hormones (TH) by activating liver gene transcription, but through a novel pathway distinct from the TH receptor. This thyromimetic effect shows tissue specificity, unlike traditional thyroid hormone actions.
Area of Science:
- Endocrinology
- Molecular Biology
- Toxicology
Background:
- Peroxisome proliferators (PP) are xenobiotics affecting various metabolic processes.
- PP exhibit biological effects similar to thyroid hormones (TH).
- PP induce TH-dependent liver gene activities in vivo and in vitro.
Purpose of the Study:
- To investigate the thyromimetic effects of PP.
- To determine the mechanism of PP-induced gene activation.
- To compare the tissue specificity of PP and TH actions.
Main Methods:
- Run-on transcription assays to assess gene activation.
- Experiments in euthyroid and thyroidectomized rats.
- Primary rat hepatocyte cultures in TH-free media.
- Assessment of PP and TH effects in rat heart and pituitary cells.
Main Results:
- PP induce liver malic enzyme (ME) and S14 gene expression, similar to TH.
- PP-mediated gene activation occurs transcriptionally.
- The thyromimetic effect of PP is not mediated by the thyroid hormone nuclear receptor.
- PP exhibit tissue-specific thyromimetic effects, differing from TH.
Conclusions:
- PP possess thyromimetic properties involving transcriptional activation of TH-dependent genes.
- PP utilize a novel signal transduction pathway independent of the TH receptor.
- PP demonstrate tissue-specific actions distinct from thyroid hormones.