Related Experiment Video

Updated: Sep 28, 2026

An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
07:01

An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma

Published on: April 17, 2013

Characterization of a thyroid hormone-mediated short-loop feedback control of TSH receptor gene in an anaplastic

S-T Chen1, J-D Lin, K-H Lin

  • 1Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan, Republic of China. stc1105@adm.cgmh.org.tw

The Journal of Endocrinology
|November 14, 2002
PubMed

Insights

Thyroid hormone receptor beta1 (TRbeta1) influences thyroid-stimulating hormone receptor (TSHR) gene expression in thyroid cancer. Its regulation by 3,5,3'-triiodothyronine (T3) depends on TRbeta1 and specific DNA sequences in the TSHR promoter.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Thyroid-stimulating hormone receptor (TSHR) gene expression is often lost in thyroid cancers due to dedifferentiation.
  • Thyroid hormone receptor beta1 (TRbeta1) is implicated in the reduced TSHR expression observed in anaplastic thyroid cancer cells.

Purpose of the Study:

  • To investigate the regulatory role of TRbeta1 in TSHR gene expression.
  • To determine the influence of 3,5,3 '-triiodothyronine (T3) on TRbeta1-mediated TSHR regulation.

Main Methods:

  • Electrophoresis mobility shift assays to assess TRbeta1 binding to the TSHR promoter.
  • Transactivation assays using reporter gene constructs with the TSHR promoter in TRbeta1-overexpressing and parental thyroid cancer cell lines.
  • Site-directed mutagenesis of the TSHR promoter to investigate the role of a cAMP response element (CRE).

Main Results:

  • TRbeta1 binds to the TSHR promoter sequence, forming heterodimers with retinoid X receptor.
  • TRbeta1 overexpression increases basal reporter gene activity, and T3 suppresses this activity in TRbeta1-overexpressing cells.
  • A mutation in the CRE site of the TSHR promoter alters T3-induced suppression, indicating sequence-specific regulation.

Conclusions:

  • TRbeta1 directly regulates TSHR gene expression.
  • The effect of T3 on TSHR gene expression is determined by the presence and activity of TRbeta1 and specific promoter DNA sequences, including a CRE.

More Related Videos

Spontaneous Murine Model of Anaplastic Thyroid Cancer05:39

Spontaneous Murine Model of Anaplastic Thyroid Cancer

Published on: February 3, 2023

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...
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...
The Thyroid Gland01:23

The Thyroid Gland

The thyroid gland is a small, butterfly-shaped gland located in the neck and covers the anterior surface of the trachea. The gland has two lateral lobes connected by a thin tissue mass called the isthmus. Internally, each lobe comprises many small spherical structures known as thyroid follicles, surrounded by a network of blood vessels.
The follicles have a central cavity lined by simple cuboidal to squamous epithelial cells called follicular cells. These cells produce the glycoprotein...
Target Cell Response to Hormones01:22

Target Cell Response to Hormones

Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Regulation of Hormone Secretion01:19

Regulation of Hormone Secretion

Regulation of hormone secretion is a finely tuned orchestration driven by various types of stimuli, encompassing neural, humoral, and hormonal signals. Environmental cues instigate neural stimuli, where action potentials traverse nerve fibers to reach their designated targets. An illustrative scenario is the body's response to stress, wherein the sympathetic nervous system releases epinephrine from the adrenal glands, inducing the well-known 'fight or flight' reaction.
Humoral stimuli,...