Thyroid hormone receptors (TRs) are transcription factors that are activated in the presence of their ligand (thyroid hormone, or TH). Their union causes the separation of corepressors and the recruitment of coactivators, with the consequent regulation of gene expression.


The main ligands of TRs are thyroid hormones (TH) T4 and T3, with a higher binding affinity for T3.

TRs can also be activated by certain endogenous and synthetic molecules, which induce active receptor conformations involved in thyroid hormone-dependent signaling pathways.


Thyroid hormone receptors (TRs) are members of the NR1 subfamily, of the large nuclear receptor superfamily (NRs), along with other receptors such as RAR, VDR, PPAR or LXR.

In turn, based on their affinity for the ligand and its mode of action, they are classified as “endocrine” and Type I receptors.

Structure and interactions

TRs have the typical nuclear receptor structure. The NTD (N-terminal transactivation) domain varies among the different isoforms. The DNA-binding domain (DBD) is highly conserved and contains two “zinc fingers” that interact with the thyroid hormone response elements (TREs) of DNA. The ligand-binding domain (LBD, in C-terminal) is comprised of twelve amphipathic helices, some of which specifically interact with coactivators and corepressors.

TR structure

In the absence of thyroid hormone (TH), TRs bind to TRE preferentially in the form of heterodimers with X retinoid receptors (RXRs), associated with corepressors that suppress basal transcriptional activity.

In the presence of TH, binding to TR modifies the conformation of the LBD region of the receptor, which causes the release of corepressors and the recruitment of coactivators, modifying the structure of chromatin and facilitating transcriptional activation of target genes.


The main active variants of the two alpha (TRα) and beta (TRβ) isoforms of TRs are expressed in:

  • TR-α1: in most tissues, mainly heart and skeletal muscle, bones, brown fat, brain and kidneys.
  • TR-β1: in most tissues, preferably liver, brain and kidney.
  • TR-β2: in the hypothalamus, anterior pituitary gland and in the developing brain.

Main functions

Among the most important functions of TRs are the regulation of metabolism and of cardiac frequency, contractility and relaxation.

Furthermore, they play a crucial role in the growth and development of organisms.

TRs in the NuRCaMeIn Network