Thyroid hormone receptor

A molecule that receives a thyroid hormone and permits it to dock on the nuclear membrane of a cell. The thyroid hormone receptors (THRs) belong to a family of nuclear receptors that function as hormone-activated transcription factors and act by modulating the expression of genes. THRs bind DNA in the absence of hormone, usually suppressing the transcription of genes. Hormone binding involves a conformational change in the receptor that lets it to activate transcription.

There are two THR genes — alpha and beta — and the primary transcript for each gene can be alternatively spliced, generating different alpha and beta receptor isoforms. Four different thyroid hormone receptors are recognized — alpha-1, alpha-2, beta-1 and beta-2. The different forms of THRs are expressed differently by tissue and by developmental stage. For example, the alpha-1 receptor is the first isoform expressed in embryonic life. And there is a great increase in expression of beta receptors in the brain shortly after birth.

The syndrome of thyroid hormone resistance is due to mutations in the beta THR gene which abolish its capacity to bind other molecules. The syndrome is characterized by a form of hypothyroidism with goiter (enlargement of the thyroid gland), elevated blood levels of T3 and thyroxine (two thyroid hormones) and normal or elevated blood levels of TSH (thyroid stimulating hormone). More than half of children with the syndrome have attention deficit disorder. The disorder is transmitted as an autosomal dominant trait.

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