Sulfation of thyroglobulin: a ubiquitous modification in vertebrates

Mammalian thyroglobulin is released by thyroid follicle cells as a sulfated glycoprotein; the sulfate residues are mostly linked to tyrosine, but they are also attached to the high-mannose carbohydrate side-chains. To decide whether sulfation of thyroglobulin is confined to mammals, representatives of other vertebrate classes were analyzed for the presence of sulfated thyroglobulin: fish (trout), amphibians (clawed toad) and birds (chicken). Mini-organs were prepared from thyroid tissue and suspended in a 35SO4-(-)-containing culture medium. Light- and electron-microscope autoradiographs prepared from the mini-organs showed that thyroid follicle cells from all species examined incorporate 35SO4-(-) and synthesize a sulfated secretory product which accumulates in the follicle lumen. The Golgi complex was detected as the primary intracellular site of sulfate organification. The 35SO4-(-)-radiolabeled secretory product of all species was shown by polyacrylamide-gel-electrophoretic analyses to consist of thyroglobulin, identified by comparison with biosynthetically 125I-labeled thyroglobulin. The results indicate that the sulfation of thyroglobulin is a ubiquitous post-translational modification observed already in the thyroglobulin of lower vertebrates. Our observations suggest that sulfation of thyroglobulin was acquired in the early stages of thyroid evolution.