The trace elements iodine and selenium exert major control function on thyroid hormone homeostasis. Appropriate production, transport to target cells, activation of prohormones to yield receptor ligands, and metabolism resulting in the termination of the hormonal signals are influenced by these two trace elements but also by dietary compounds such as flavonoids. Flavonoids, ubiquitous secondary metabolites of plants and their synthetic derivatives such as EMD 21388 interfere with hormone binding to transthyretin and activation by the selenoenzyme Type I 5'deiodinase. The resulting alterations of free thyroid hormone fractions in serum effect pituitary feedback regulation, hormone action and elimination. Selenium dependent regulation of expression of Type I 5'deiodinase and glutathione peroxidase was studied in the porcine kidney epithelial cell line LLC-PK1 at the enzyme activity, protein and steady-state mRNA levels. A cellular hierarchy of selenite utilization with preferential incorporation into Type I 5'deiodinase compared to glutathione peroxidase was found under limiting selenite supply. These mechanisms together with hierarchic selenium redistribution between brain and endocrine organs might contribute to maintain thyroid hormone homeostasis during development and pathophysiological situations.