Thyroid hormone receptor

[4] Two of these, the DNA-binding (DBD) and hinge domains, are involved in the ability of the receptor to bind hormone response elements (HREs).

Thyroid hormone receptors play critical roles in the regulation of metabolism, heart rate, and development of organisms.

Once RXRs bind ligand, they undergo conformational changes that reduce their affinity for corepressors—allowing them to attract coactivators to the transcription site.

In the absence of hormone, TR forms a complex with corepressor proteins such as nuclear receptor co-repressor 1 (N-CoR) and 2 (N-CoR2).

Binding of thyroid hormone results in a conformational change in helix 12 of the TR transactivation domain, which displaces the corepressors from the receptor/DNA complex.

The protein products from this process drive the changes in cell function observed in the presence of thyroid hormone.

In contrast, more recently, a specific molecular mechanism for TR-β signaling through the PI3 kinase has been identified,[13] which allowed scientists to obtain direct genetic evidence for the involvement of TR-β signaling through the PI3 kinase in brain development[13] and metabolism,[14] two of the primary physiological effects of thyroid hormone action.

In a healthy individual, the TR-β2 expressed in the pituitary gland plays a major role in regulating thyroid-stimulating hormone (TSH) levels through negative feedback.

The elimination of the negative feedback loop results in the heightened levels of thyroid hormone presented by patients with this condition.

This can make TR-α resistance more difficult to diagnose because patients do not typically present with elevations in thyroid hormone concentration.

Common symptoms of TR mutation include: Treating patients with hypothyroidism caused by the absence of functional TRs is difficult.

For those whose conditions mimic hypothyroidism, prescribing normal thyroid hormone doses may not remedy the symptoms they are experiencing.

Individuals with a THRB or THRA mutation have less receptors that are able to bind ligand, and a corresponding drop in tissue responsiveness to thyroid hormone.

For this reason, physicians may prescribe higher doses of the hormone to increase the probability that the ligand will reach a TR that is functional.

Prescribing thyroid hormone in any dose to patients presenting with symptoms mimicking hyperthyroidism does not improve the condition.

By blocking the ability of receptors to bind adrenaline, beta-blockers have been observed to alleviate symptoms of anxiety, increased blood pressure, and irregular heartbeat, amongst others.