Related Experiment Video
Updated: Jul 10, 2026
In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse
Published on: October 6, 2023
Thyroid hormone (T3) rapidly activates p38 and AMPK in skeletal muscle in vivo
Isabella Irrcher1, Donald R Walkinshaw, Treacey E Sheehan
1Department of Biology, York University, Toronto, Ontario, Canada.
Abstract:
Thyroid hormone (T(3)) regulates the function of many tissues within the body. The effects of T(3) have largely been attributed to the modulation of thyroid hormone receptor-dependent gene transcription. However, nongenomic actions of T(3) via the initiation of signaling events are emerging in a number of cell types. This study investigated the ability of short-term T(3) treatment to phosphorylate and, therefore, activate signaling proteins in rat tissues in vivo. The kinases investigated included p38, AMP-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK) 1/2. Following 2 h of T(3) treatment, p38 and AMPK phosphorylation was increased in both the slow-twitch soleus and the fast-twitch plantaris muscles. In contrast, ERK1/2 was not activated in either muscle type. Neither p38 nor AMPK was affected in heart. However, AMPK activation was decreased by T(3) in liver. ERK1/2 activation was decreased by T(3) in heart, but increased in liver. Possible downstream consequences of T(3)-induced kinase phosphorylation were investigated by measuring cAMP response element binding protein (CREB) and thyroid hormone receptor DNA binding, as well as peroxisome proliferator-activated receptor-alpha coactivator-1 mRNA levels. Protein DNA binding to the cAMP or thyroid hormone response elements was unaltered by T(3). However, peroxisome proliferator-activated receptor-alpha coactivator-1 mRNA expression was increased following 12 h of T(3) treatment in soleus. These data are the first to characterize the effects of T(3) treatment on kinase phosphorylation in vivo. We show that T(3) rapidly modifies kinase activity in a tissue-specific fashion. Moreover, the T(3)-induced phosphorylation of p38 and AMPK in both slow- and fast-twitch skeletal muscles suggests that these events may be important in mediating hormone-induced increases in mitochondrial biogenesis in skeletal muscle.
Insights
Thyroid hormone (T3) rapidly activates signaling proteins like p38 and AMPK in rat muscles, suggesting a role in mitochondrial biogenesis. This study reveals tissue-specific, nongenomic effects of T3 beyond gene transcription.
Area of Science:
- Endocrinology
- Molecular Biology
- Physiology
Background:
- Thyroid hormone (T3) primarily influences cellular function through genomic mechanisms involving thyroid hormone receptors.
- Emerging evidence suggests T3 also exerts rapid, nongenomic effects by initiating intracellular signaling cascades.
- Understanding these nongenomic actions is crucial for a comprehensive view of T3's physiological roles.
Purpose of the Study:
- To investigate the in vivo effects of short-term T3 treatment on the phosphorylation and activation of key signaling kinases (p38, AMPK, ERK1/2) in various rat tissues.
- To explore potential downstream consequences of T3-induced kinase activation on gene expression and protein-DNA binding.
Main Methods:
- Rats were treated with T3 for 2 hours, and tissue samples (soleus, plantaris, heart, liver) were analyzed for kinase phosphorylation.
- Western blotting was used to assess the phosphorylation status of p38, AMPK, and ERK1/2.
- Levels of CREB and thyroid hormone receptor DNA binding, along with PGC-1α mRNA, were measured to assess downstream effects.
Main Results:
- T3 treatment significantly increased phosphorylation of p38 and AMPK in both slow-twitch (soleus) and fast-twitch (plantaris) skeletal muscles.
- ERK1/2 activation was not observed in skeletal muscles but showed differential regulation in heart (decreased) and liver (increased).
- AMPK activation decreased in the liver, while PGC-1α mRNA expression increased in the soleus muscle after 12 hours of T3 treatment.
Conclusions:
- T3 rapidly induces tissue-specific changes in kinase activity in vivo, demonstrating significant nongenomic effects.
- The activation of p38 and AMPK in skeletal muscle suggests a role for these signaling pathways in mediating T3-induced mitochondrial biogenesis.
- These findings provide novel insights into the rapid, signaling-mediated actions of thyroid hormone distinct from its classical genomic effects.
Related Concept Videos
01:18Functions of Thyroid Hormones
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...
01:20Synthesis and Regulation of Thyroid Hormones
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...
01:25cAMP-dependent Protein Kinase Pathways
01:22PI3K/mTOR/AKT Signaling Pathway
01:17Hormones and Bone Tissue
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
01:27Hyperthyroidism II: Pathophysiology