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Functions of Thyroid Hormones01:18

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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: Accurately Assessing Thyroid Hormone-Driven Motor Alterations in Mouse
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Alternative ligands for thyroid hormone receptors.

Iván Lazcano1, Gabriela Hernández-Puga2, Juan Pablo Robles3

  • 1Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, Qro, Mexico; Departamento de Investigación Biomédica, Facultad de Medicina, Universidad Autónoma de Querétaro, Qro, Mexico.

Molecular and Cellular Endocrinology
|May 18, 2019
PubMed
Summary

Thyroid hormone receptors (TRs) regulate gene expression. This review explores how alternative ligands, including endogenous and synthetic molecules, interact with TRs to modulate thyroid hormone signaling pathways.

Keywords:
3,5-T2Alternative ligandTRIACThyroid hormone analogsThyroid hormone receptorsThyroid hormones

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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Genetics

Background:

  • Thyroid hormone receptors (TRs) are crucial ligand-dependent transcription factors.
  • TRs regulate diverse physiological processes by activating or repressing gene transcription.
  • 3,3',5-L-triiodothyronine is the primary cognate ligand for TRs.

Purpose of the Study:

  • To review current knowledge on alternative ligands binding to TRs.
  • To discuss the molecular interactions between TRs and various ligands.
  • To highlight the role of these interactions in thyroid hormone signaling and therapeutic development.

Main Methods:

  • Literature review of studies on TR-ligand interactions.
  • Analysis of research on endogenous and synthetic TR ligands.
  • Examination of molecular mechanisms of TR activation and gene regulation.

Main Results:

  • TRs can be activated by alternative ligands beyond 3,3',5-L-triiodothyronine.
  • Endogenous molecules like 3,5-diiodo-L-thyronine and 3,5,3'-triiodothyroacetic acid modulate TR activity.
  • Synthetic thyromimetics and endocrine disruptors reveal specific TR isoform interactions and binding site residues.

Conclusions:

  • Alternative ligands induce diverse TR conformations, influencing thyroid hormone signaling.
  • Understanding TR-ligand interactions is key for developing targeted therapies for thyroid disorders.
  • Ligand design can achieve tissue-specific regulation of TR activity.