With the isolation of thyroxin by Kendall in 1914 and its synthesis by Harington and Barger in 1927, the physiologically active component of the thyroid gland appeared to have been identified. The biosynthesis of this compound apparently involves the iodination of tyrosine to monoiodotyrosine and diiodotyrosine, the condensation of two molecules of the latter compound yielding thyroxin, which is then stored in the thyroid in the form of thyroglobulin. As the need for thyroid hormone arises, the thyroglobulin is broken down by a proteolytic enzyme to biologically active fragments of sufficiently low molecular weight to diffuse out of the thyroid follicles. In the plasma, these become rather loosely bound to protein to form the greater portion of the protein-bound iodine moiety.
Until recently it was felt that thyroxin was the only biologically active component of the protein-bound iodine. However, in 1951 Gross and Leblanc, using autoradiographic and chromatographic techniques, discovered
THE THYROID HORMONE. JAMA. 1954;155(11):980-981. doi:10.1001/jama.1954.03690290030009