REGULATION OF THYROID FUNCTION T4 AND T3 KINETICS

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Past and proposed work in this laboratory have included the following major areas of clinical and basic research: metabolism, protein binding and peripheral effects of the thyroid hormones (TH); regulation of TSH secretion; effects of iodine on thyroid function in man and rodents; and immunological aspects of thyroid pathophysiology. A synthetic flavonoid, EMD 21388 (F), which inhibits the serum protein binding (TBPA) of the TH and 5'- deiodinase activity (5'-D) in vitro will be utilized to study, in the rat, the in vivo effects of rapid displacement of the TH from their major serum binding protein (TBPA) in peripheral tissues, the possible thyromimetic effects of F in vivo and in vitro (using GH producing tumor cell lines), and the possible in vivo and in vitro inhibitory effects of F on 5'-D. Starvation and other experimental conditions in the rat are associated with the appearance of serum TBG (rTBG), and preliminary studies suggest an enhanced response in females compared to males. This will be further investigated to determine the possible etiology of this finding. The prevalence of Familial Dysalbuminemic Hyperthyroximenia (FDH), which appears to be relatively common, especially in Puerto Rican families, will be determined by studying families of newborns whose serum T4 concentration is at least 2SD above the mean. The role of iodine intake on the prevalence of thyroid dysfunction in the elderly and in the pathogenesis of autoimmune thyroid diseases in man and in the diabetes prone BB/Wor rat will continue to be addressed. New immunosuppressant drugs (thalidomide and ciamexone) will be used in an attempt to prevent the occurrence of spontaneous and iodine induced lymphocytic thyroiditis (LT) in the BB/Wor rat. This model will also be used to determine whether, as in humans, transient LT is common during the post partum period. Finally, preliminary retrospective studies suggest that chronic levothyroxine therapy for hypothyroidism and for TSH suppression in premenopausal women enhances bone loss. A prospective study is now planned to confirm these observations. The overall aims of this proposal is to provide further information on the binding and peripheral metabolism and effects of the TH and to further delineate the role of iodine and class II (Ia) antigen in the etiology of autoimmune thyroid disease in man and rat.