Thyroid hormone deiodination

The enzymatic deiodination of thyroid hormone is an important process since it concerns- among other things- the regulation of thyromimetic activity at the site of the target organ. To understand the mechanism of this regulation it is necessary to have a detailed knowledge of the mode of action of the enzyme(s) involved in the metabolism of thyroid hormone. My investigations of the deiodination of iodothyronines at the subcellular level, forming the basis of this thesis, are described in the appendix papers. It is not intended to deal in extenso with the technical aspects of my studies in the preceeding chapters. Rather it will be attempted to give a general review of the literature including- with some emphasis -my own work. Though not directly related to the subject of this thesis, the biosynthesis of thyroid hormone in the thyroid gland is treated in the first chapter. This is done because of possible similarities between thyroid hormone iodination and deiodination pathways, which are suggested by the finding that some drugs inhibit both processes. In the same chapter the relationship between iodothyronine structure and biological potency is described to illustrate that indeed deiodination has a dramatic effect on the activity of thyroid hormone. Besides deiodination, other pathways of metabolism are also considered. The second chapter concerns the in vivo investigation of thyroid hormone deiodination under physiological and pathological conditions. This includes the effects of internal and external factors which affect deiodination, such as dietary intake, drugs, stress and illness. Since much work has been done to find an explanation for the effect of calorie restriction on deiodination at the molecular level, the role of the diet is emphasized. This appears particularly important since nutritional status must be considered to contribute to the change in thyroid hormone metabolism found in other situations, for example in systemic illness. The in vitro observations of the enzymatic deiodination of thyroid hormone are described in chapter 3. A distinction has been made between (early) reports on the analysis of iodide production using chromatography, and (more recent) studies dealing with the detection of specific metabolites, often by means of radioimmunoassay. My investigations which belong to the latter category are presented in the appendix papers