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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...
Functions of Thyroid Hormones01:18

Functions of Thyroid Hormones

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.
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
Hypothyroidism II: Pathophysiology01:23

Hypothyroidism II: Pathophysiology

Hypothyroidism is a disorder characterized by insufficient production of thyroid hormones, which regulate metabolism, energy balance, and multiple organ systems.TypesHypothyroidism is classified based on the level of dysfunction. Primary hypothyroidism results from intrinsic thyroid gland dysfunction, causing reduced hormone production despite normal or increased stimulation. Secondary hypothyroidism arises from inadequate thyroid-stimulating hormone (TSH) secretion by the pituitary. Tertiary...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Hyperthyroidism II: Pathophysiology01:27

Hyperthyroidism II: Pathophysiology

Hyperthyroidism is a hypermetabolic state caused by elevated levels of thyroid hormones, triiodothyronine (T3) and thyroxine (T4). It results from dysregulation at the thyroid, pituitary, or immune system level and affects multiple organ systems.PathophysiologyThe most common cause of hyperthyroidism is Graves’ disease, an autoimmune disorder in which antibodies, specifically thyroid-stimulating antibodies (TSAb), a subtype of TSH receptor antibodies (TRAb), bind to and activate TSH receptors...
Graves Disease II: Pathophysiology01:24

Graves Disease II: Pathophysiology

Graves’ disease is an autoimmune disorder characterized by the production of thyroid-stimulating immunoglobulins (TSI) that activate TSH receptors, leading to excessive synthesis and release of thyroid hormones (T3 and T4) and resulting in hyperthyroidism.Among all causes of hyperthyroidism, Graves’ disease is the most common and can happen at any age, though it is more frequent in women. It produces a hypermetabolic state with features such as weight loss, tachycardia, tremor, and heat...

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Related Experiment Video

Updated: May 27, 2026

Analysis of Translation Initiation During Stress Conditions by Polysome Profiling
10:59

Analysis of Translation Initiation During Stress Conditions by Polysome Profiling

Published on: May 19, 2014

Endoplasmic reticulum stress decreases intracellular thyroid hormone activation via an eIF2a-mediated decrease in

Rafael Arrojo E Drigo1, Tatiana L Fonseca, Melany Castillo

  • 1Division of Endocrinology, Diabetes and Metabolism, University of Miami Miller School of Medicine Miami, Florida 33136, USA.

Molecular Endocrinology (Baltimore, Md.)
|November 5, 2011
PubMed
Summary
This summary is machine-generated.

Endoplasmic reticulum (ER) stress rapidly reduces type 2 deiodinase (D2) activity by decreasing its synthesis and increasing proteasomal degradation. This mechanism explains D2 loss in conditions like cystic fibrosis.

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Last Updated: May 27, 2026

Analysis of Translation Initiation During Stress Conditions by Polysome Profiling
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Published on: May 19, 2014

In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse
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In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse

Published on: October 6, 2023

Area of Science:

  • Biochemistry
  • Cell Biology
  • Endocrinology

Background:

  • Cells activate endoplasmic reticulum (ER) stress responses to manage unfolded proteins.
  • ER-resident type 2 deiodinase (D2) regulates thyroid hormone metabolism and is normally degraded via proteasomes.
  • ER stress pathways involve protein translation inhibition, enhanced folding, and degradation of misfolded proteins.

Purpose of the Study:

  • To investigate if ER-associated degradation impacts type 2 deiodinase (D2) under ER stress conditions.
  • To determine the mechanism behind D2 activity loss during ER stress.
  • To explore the role of eukaryotic initiation factor 2 (eIF2) in ER stress-induced D2 regulation.

Main Methods:

  • Induction of ER stress using thapsigargin or tunicamycin in cells expressing endogenous or exogenous D2.
  • Measurement of D2 activity, D2 mRNA levels, and protein synthesis using [(35)S]methionine labeling.
  • Inhibition of proteasomal degradation with MG-132 and manipulation of eIF2 activity.

Main Results:

  • ER stress significantly reduced D2 activity (up to 70%) without altering D2 mRNA levels.
  • D2 activity was absent in primary human airway cells experiencing ER stress due to cystic fibrosis.
  • ER stress decreased D2 synthesis and enhanced its proteasomal degradation, a process mediated by eIF2.

Conclusions:

  • D2 is selectively lost during ER stress through a mechanism involving decreased synthesis and sustained proteasomal degradation.
  • The eIF2 pathway is crucial in mediating the ER stress-induced reduction of D2 activity.
  • This selective loss of D2 explains its absence in ER-stressed airway cells associated with cystic fibrosis.