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Related Concept Videos

Synthesis and Regulation of Thyroid Hormones01:20

Synthesis and Regulation of Thyroid Hormones

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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.
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The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
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Author Spotlight: In Vivo Assessment of Thyroid Hormone Disruption Using the THAI Mouse Model
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Identifying reference chemicals for thyroid bioactivity screening.

Susanna Wegner1, Patience Browne2, David Dix2

  • 1Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN, United States.

Reproductive Toxicology (Elmsford, N.Y.)
|September 4, 2016
PubMed
Summary
This summary is machine-generated.

This study identified 34 reference chemicals, including 29 active and five inactive, to validate new high-throughput screening assays for thyroid bioactivity. These chemicals will aid in assessing potential endocrine disruptors affecting thyroid function.

Keywords:
Amphibian metamorphosis assayPerformance-based validationRat pubertal assayReference chemicalsThyroid

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Area of Science:

  • Environmental toxicology
  • Endocrinology
  • Chemical screening

Background:

  • The U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program (EDSP) utilizes 'Tier 1' screening assays.
  • Thyroid bioactivity is a key area of concern for endocrine disruption.
  • Validation of alternative assays is crucial for efficient chemical screening.

Purpose of the Study:

  • To select and characterize reference chemicals based on their known thyroid bioactivity.
  • To provide a set of chemicals for the performance-based validation of novel, high-throughput screening assays.
  • To support the development of more efficient methods for identifying thyroid-active chemicals.

Main Methods:

  • Reference chemicals were chosen based on results from established 'Tier 1' screening assays.
  • Active chemicals demonstrated significant effects on thyroid-responsive endpoints in amphibian metamorphosis and pubertal rodent assays.
  • Inactive chemicals showed no significant effects in these assays or in literature reviews.

Main Results:

  • A total of 34 reference chemicals were selected: 29 classified as active and five as inactive.
  • Active chemicals met criteria for thyroid bioactivity, with mechanistic data considered when direct effects were not observed.
  • Inactive chemicals lacked significant thyroid-responsive effects in multiple assays and databases.

Conclusions:

  • The curated set of 34 reference chemicals is suitable for validating alternative, high-throughput screening assays for thyroid bioactivity.
  • These chemicals will serve as a critical tool for assessing the performance of new screening methodologies.
  • The study contributes to the development of more robust and efficient endocrine disruptor screening processes.