Iodination of thyroglobulin. An intracellular or extracellular process?

The location in the thyroid follicle of the iodination of thyroglobulin has been a matter of debate for several decades. This problem is not a question of mere academic interest. Knowledge of the locus--or loci--of iodination is necessary for a full understanding of the mechanisms involved in thyroid-hormone synthesis and release. In the discussion about this problem 3 fundamentally different views have been--and still are--advocated. The first view implies that the site of iodination is the follicle lumen, the second that iodination is an intracellular process restricted to some organelle(s) in the follicle cells and the third that iodination occurs at the interface between the follicle cells and the follicle lumen. Below I will survey the major observations on which these different opinions are based and discuss the validity of the interpretations.