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Related Concept Videos

Synthesis and Regulation of Thyroid Hormones01:20

Synthesis and Regulation of Thyroid Hormones

Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
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Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...

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Evaluating the performance of multi-omics integration: a thyroid toxicity case study.

Sebastian Canzler1, Kristin Schubert2, Ulrike E Rolle-Kampczyk2

  • 1Helmholtz Centre for Environmental Research, UFZ, 04318, Leipzig, Germany. sebastian.canzler@ufz.de.

Archives of Toxicology
|October 23, 2024
PubMed
Summary

Multi-omics data integration enhances toxicological research by providing a comprehensive molecular response profile. This study demonstrates its superiority over single-omics for thyroid toxicity assessment in rats.

Keywords:
Chemical exposureData integrationMulti-omicsRisk assessmentToxicology

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Area of Science:

  • Systems toxicology and regulatory risk assessment.
  • Multi-omics data integration for chemical exposure analysis.

Background:

  • Previous reviews highlighted the potential of multi-omics but noted a scarcity of high-quality, multi-layered datasets in toxicology.
  • Limitations in existing data hindered full assessment of integration benefits and individual omics contributions.
  • Best practices for experimental design, data acquisition, and integration were previously established.

Purpose of the Study:

  • To conduct a best-practice compliant multi-omics study on thyroid toxicity.
  • To compare the efficacy of multi-omics versus single-omics approaches.
  • To evaluate the contribution of different omics layers and their integration with clinical data.

Main Methods:

  • A 28-day plus 14-day recovery oral rat toxicity study using Propylthiouracil (PTU) and Phenytoin to induce thyroid toxicity.
  • Collection of clinical and histopathological data.
  • Acquisition of six omics layers (transcriptome, proteome, phosphoproteome, metabolome) from plasma, thyroid, and liver.

Main Results:

  • Multi-omics approach demonstrated superiority over single-omics in identifying regulatory pathway responses.
  • Integration of omics data with clinical and histopathological parameters improved data interpretation.
  • Multi-omics integration suggested the involvement of non-coding RNAs in post-transcriptional regulation and facilitated grouping analysis.

Conclusions:

  • Multi-omics data integration is a powerful tool for systems toxicology, offering deeper insights than single-omics.
  • Adherence to best practices is crucial for robust multi-omics studies in toxicology.
  • This study provides a framework for assessing the contribution of individual and combined omics layers in toxicological assessments.