| The thyroid hormone-receptor complex generally binds to DNA as a heterodimer, each partner of the pair to a so called half site. The most common dimerization partner for the T3 receptor is the receptor for cis- retinoic acid (RXR). The complex of the receptor devoid of the hormone and the dimerization partner suppresses the expression of the target gene. Binding of T3 to the receptor not only reverses the suppression but boosts the expression of the gene to a higher than basal state. The requirements of the nucleic acid arrangements at the DNA level is amazingly loose. The half-sites are variants of the AGGTCA, either as direct or inverted repeats. Within the last several years studies have shown that the initiating complex has become even more complex than first supposed. It is now clear that other proteins binding to the receptor-dimer complex interact with the promoter region of the target gene to either enhance or diminish gene expression. Those acting in a positive direction are designated "co-activators" and those in a negative sense, "co-repressors". The molecular mechanisms of thyroid hormone action have recently been reviewed (5,6). |
