[Molecular biology and laboratory diagnosis of hypothalamic-pituitary-thyroid axis].

Recent developments in molecular biology have brought dramatic changes in laboratory medicine. Applications of molecular biology techniques have made it possible to make etiological diagnosis and produce recombinant proteins for reagents. Laboratory investigations of molecular biology in the hypothalamic-pituitary-thyroid axis include TRH gene, TRH effect, TSH gene, TSH receptor and its autoantibodies, thyroid peroxidase and thyroglobulin and their autoantibodies, thyroxine (T4) binding protein genes, deiodination of T4, thyroid hormone receptor, oncogenes of thyroid etc. The following developments are reviewed. 1) Human TSH (hTSH) beta gene and its abnormality: Two types of mutations of hTSH beta gene have been found in patients with hereditary isolated TSH deficiency. DNA diagnosis and genetic counseling are now being performed. 2) Structure and function of TSH receptor: The primary structure of hTSH receptor was identified from its gene. Relationships between its structure and function have been investigated using site specific mutagenesis and synthetic short peptides. 3) Thyroid hormone receptor gene and its abnormality: The thyroid hormone receptor gene has been successfully cloned. Several mutations of the gene have been demonstrated in patients with thyroid hormone resistance. 4) Application of recombinant hTSH (r-hTSH):r-hTSH has been produced in CHO cells. Immunological and biological properties of r-hTSH are similar to those of authentic pituitary hTSH. Clinical application of r-hTSH is now in progress.