Hypothalamic TRH cell

Hypothalamic TRH cell

Thyroid releasing hormone (TRH) cells are located in the hypothalamus. The production of the hormone TRH is controlled by neuronal input from other brain centres and by thyroid hormone. The promotor of the TRH gene (and the TSH gene) contains a so-called thyroid response element (TRE), to which the thyroid hormone receptor can bind.

About thyroid hormone receptors (see graphic below):

Thyroid hormone receptors function as hormone-activated transcription factors and thus as modulators of gene expression.

The receptors consist of three functional domains:

The thyroid hormone receptors bind to a short DNA sequence known as positive thyroid responsive elements (TREs). The thyroid hormone receptors can bind to a TRE as monomer, as homodimer or as heterodimer with the retinoid X receptor (RXR). In the absence of TH, the ligand-free thyroid hormone receptor binds DNA as a heterodimer with RXR. This complex interacts with coactivator molecules and stimulates transcription. TH binding is associated with a conformational change, which allows corepressor molecules to bind instead of coactivators. The corepressor complex associated with the TH-bound receptor inhibits transcription of genes.

The human TSH and TRH gene have a TRE in their promotor region, meaning that binding of ligand-free thyroid hormone receptor stimulates transcription. Conversely, binding of TH to its receptor represses transcription of TSH or TRH. This explains the negative feedback of thyroid hormone on TSH and TRH expression and secretion.