Role of cellular transport systems in the regulation of thyroid hormone bioavailability

In this thesis the relevance of the plasma and plasmamembrane transport of thyroid hormone in its activation and metabolism is described. All early studies in our laboratory on transport of thyroid hormone over the plasma membrane were performed with rat hepatocytes in primary culture, with a medium containing only 0.5 or 1% albumin, in fact in no way comparable with plasma or interstitial fluid, the physiological medium. Plasma contains three thyroid hormone binding proteins, which bind more than 99.97% of the circulating T4. About 75% of this T4 is bound to thyroxine binding globulin, 15% to thyroxine binding prealbumin and 10% to albumin. Because there existed (and still exists) a controversy in literature whether different concentrations of binding proteins influence uptake of hormone into tissue cells, we have tried to resolve this problem by comparing the results of tracer kinetic studies in subjects with an autosomal dominant inherited elevated binding of T4 to serum proteins with similar data obtained in normals. In chapter ill it was shown that a strongly elevated binding of T 4 in serum does not lead to a change in free hormone concentration or a change in disposal rate of T4, which fmding makes a role of these binding proteins in the tissue uptake of thyroid hormone unlikely. Furthermore, it was shown that this biochemical syndrome, originally described by us, is caused by albumin with high affinity for T 4, and that this albumin is also present in low concentrations in normals. In later studies in the literature this syndrome is known as "familial dysalbuminemic hyperthyroxinemia" (FDH).