Related Experiment Video
Updated: Jun 17, 2026
An Ex vivo Culture System to Study Thyroid Development
Published on: June 6, 2014
Calcium signaling of thyrocytes is modulated by TSH through calcium binding protein expression
Stephan Lorenz1, Markus Eszlinger, Ralf Paschke
1III. Medical Department, Faculty of Medicine, University of Leipzig, D-04103 Leipzig, Germany.
Abstract:
TSH is an important stimulus to maintain thyroid epithelial differentiation. Impairment of TSH signal transduction can cause thyroid pathologies such as hot nodules, goiter and hyperthyroidism. In a gene expression study in Fischer rat thyroid cells (FRTL-5) using cDNA microarrays we found a TSH-dependent regulation of several calcium binding proteins, S100A4, S100A6 and annexin A6. Expression of these genes in FRTL-5 and regulation by TSH was confirmed with LightCycler qPCR and Western blotting. The differential expression of S100A4 was confirmed for cultured primary human thyrocytes. Calcium-imaging experiments showed that prestimulation with TSH attenuates ATP-elicited P2Y-mediated calcium signaling. Experiments with thapsigargin, TSH and calcium-free perfusion excluded an involvement of other purinergic receptors or an involvement of SERCA regulation. Instead, we find a correlation between S100A4 expression and the effects of TSH on calcium signaling. Overexpression of S100A4 in FRTL-5 and shRNA-mediated knockdown of S100A4 in follicular thyroid cancer cells (FTC133) confirm the ability of S100A4 to attenuate calcium signals. Under repeated stimulations with ATP the calcium retention of these cells is also modulated by S100A4, suggesting a role of S100A4 as calcium buffering protein. As a biological consequence of S100A4 overexpression we detected reduced ATP-stimulated cFos induction. Taken together, the results suggest that S100A4 and other calcium binding proteins are part of a signaling network connecting TSH signaling to calcium-mediated events which play a role in thyroid physiology like H2O2 production or even thyroid cancer.
Insights
Thyroid-stimulating hormone (TSH) regulates calcium signaling via S100A4, a calcium-binding protein. This finding reveals a new pathway in thyroid cell function and disease, impacting thyroid cancer research.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Signaling
Background:
- Thyroid-stimulating hormone (TSH) is crucial for thyroid epithelial cell differentiation and function.
- Dysregulation of TSH signaling is implicated in thyroid pathologies like goiter and hyperthyroidism.
- Calcium signaling plays a vital role in various cellular processes within the thyroid.
Purpose of the Study:
- To investigate the TSH-dependent regulation of calcium-binding proteins in thyroid cells.
- To elucidate the role of S100A4 in mediating TSH's effects on calcium signaling.
- To explore the implications of S100A4 in thyroid physiology and disease.
Main Methods:
- Gene expression profiling using cDNA microarrays in Fischer rat thyroid cells (FRTL-5).
- Quantitative PCR (qPCR) and Western blotting to confirm gene and protein expression.
- Calcium imaging experiments and functional assays (overexpression, knockdown) to assess S100A4's role in calcium signaling and cellular responses.
Main Results:
- TSH regulates the expression of calcium-binding proteins S100A4, S100A6, and annexin A6.
- S100A4 expression is inversely correlated with TSH's effect on ATP-induced calcium signaling.
- S100A4 overexpression attenuates calcium signals and modulates cellular responses, suggesting a calcium-buffering role.
- S100A4 influences downstream signaling pathways, such as c-Fos induction.
Conclusions:
- S100A4 is a key mediator connecting TSH signaling to calcium-dependent cellular events in thyroid cells.
- This TSH-S100A4-calcium signaling axis is relevant to normal thyroid function and potentially thyroid cancer.
- S100A4 represents a novel target for understanding and potentially treating thyroid disorders.
More Related Videos
13:40Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms
Published on: July 7, 2011
11:25Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins
Published on: October 4, 2017
Related Concept Videos
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...
00:51Synthesis and Functions of Calcitonin
The exact mechanisms by which calcitonin operates in calcium homeostasis remain elusive, but its significance is evident in several vital...
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...
01:17Hormones 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...
01:16Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:21Skeleton and Calcium Homeostasis