Serum thyroglobulin and thyroid cancer.

Thyroglobulin is a large glycosylated protein (MW 660000 daltons) which is synthesised and secreted by the thyroid cell into the follicular lumen. In the thyroglobulin molecule the iodotyrosines undergo oxidative coupling to form the iodothyronines thyroxine (T4) and triiodothyronine (T3). Production of thyroid hormones results from micropinocytosis of iodinated thyroglobulin from the colloid into the thyroid cell and its hydrolysis by lysosymal enzymes. The resulting T4 and T3 diffuse across the basal membrane into the blood stream whilst iodotyrosines are de-iodinated and the iodine recycled. Thyroglobulin thus acts as the template for thyroid hormone synthesis and a storage form of inactive thyroid hormones and iodine. Thyroid function and activity are under the positive control of thyrotrophin (TSH) which stimulates many steps of thyroid cell metabolism including protein synthesis, iodothyronine synthesis, thyroglobulin secretion into the follicular lumen, and replacement of micropinocytosis of thyroglobulin by massive colloid macropinocytosis [1]. The action of TSH on the thyroid cell is mediated via adenylate cyclase activation and recent work has shown that transcription of the thyroglobulin gene is regulated by cyclic AMP [2].