Cellular binding proteins of thyroid hormones.

Cellular binding proteins of thyroid hormones are present in the cell nucleus, cytosol, cell membrane, and mitochondria. While nuclear binding is proven to mediate hormone action, the exact roles of the other binding sites remain to be established. Nuclear receptor associates with DNA, core histone, and nuclear matrix and preferentially distributes in transcriptionally active chromatin due to interaction with H1 histone. Of particular importance is the binding of nuclear receptor to specific DNA sequences of target genes, termed thyroid-responsive elements. The binding is stabilized by non-receptor nuclear protein. Upon binding thyroid hormone, nuclear receptor is activated through alterations in the steric configuration, leading to changes in the rate of transcription of the target genes. Multiple nuclear receptor forms exist with likely distinct functional roles. Cytosolic thyroid hormone binding proteins are also heterogeneous. One form is under the control of cell metabolism (NADP and NADPH) and it may have a role in transport of the hormone to mitochondria and nucleus. Membrane-linked thyroid hormone binding proteins may have dual functional roles: one is to mediate hormone action and the other is to support active uptake of hormones by cells. Mitochondrial function may be regulated by thyroid hormone through mitochondrial binding sites in cooperation with nuclear receptor-mediated pathway. Further studies are required to elucidate the exact functional roles of non nuclear thyroid hormone binding proteins.