Thyroid hormones
The thyroid hormones function via a well-studied set of nuclear receptors, termed the thyroid hormone receptors. These receptors, together with corepressor molecules, bind DNA regions called thyroid hormone response elements (TREs) near genes. This receptor-corepressor-DNA complex can block gene transcription. Triiodothyronine (T3), which is the active form of thyroxine(T4), goes on to bind to receptors. The deiodinase catalyzed reaction removes an iodine atom from the 5' position of the outer aromatic ring of Thyroxine's (T4) structure. When triiodothyronine (T3) binds a receptor, it induces a conformational change in the receptor, displacing the corepressor from the complex. This leads to recruitment of coactivator proteins and RNA polymerase, activating transcription of the gene.
Antithyroid autoantibodies
Anti-thyroid peroxidase (anti-TPO) antibodies are specific for the autoantigen TPO, a 105kDa glycoprotein that catalyses iodine oxidation and thyroglobulin tyrosyl iodination reactions in the thyroid gland. Most antibodies produced are directed to conformational epitopes of the immunogenic carboxyl-terminal region of the TPO protein, although antibodies to linear epitopes have been seen. Anti-TPO antibodies are the most common anti-thyroid autoantibody, present in approximately 90% of Hashimoto's thyroiditis, 75% of Graves' disease and 10-20% of nodular goitre or thyroid carcinoma. Also, 10-15% of normal individuals can have high level anti-TPO antibody titres. High serum antibodies are found in active phase chronic autoimmune thyroiditis. Thus, an antibody titer can be used to assess disease activity in patients that have developed such antibodies. The majority of anti-TPO antibodies are produced by thyroid infiltrating lymphocytes, with minor contributions from lymph nodes and the bone marrow. They cause thyroid cell damage by complement activation and antibody dependent cell cytotoxicity. However, anti-TPO antibodies are not believed to contribute to the destruction of the thyroid.