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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK018919-17
Application #
3226223
Study Section
Endocrinology Study Section (END)
Project Start
1978-12-01
Project End
1993-11-30
Budget Start
1990-12-01
Budget End
1991-11-30
Support Year
17
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655
Eng, P H; Cardona, G R; Previti, M C et al. (2001) Regulation of the sodium iodide symporter by iodide in FRTL-5 cells. Eur J Endocrinol 144:139-44
Marqusee, E; Braverman, L E; Lawrence, J E et al. (2000) The effect of droloxifene and estrogen on thyroid function in postmenopausal women. J Clin Endocrinol Metab 85:4407-10
Lawrence, J E; Lamm, S H; Pino, S et al. (2000) The effect of short-term low-dose perchlorate on various aspects of thyroid function. Thyroid 10:659-63
Roti, E; Gardini, E; Magotti, M G et al. (1999) Are thyroid function tests too frequently and inappropriately requested? J Endocrinol Invest 22:184-90
Minelli, R; Braverman, L E; Valli, M A et al. (1999) Recombinant interferon alpha (rIFN-alpha) does not potentiate the effect of iodine excess on the development of thyroid abnormalities in patients with HCV chronic active hepatitis. Clin Endocrinol (Oxf) 50:95-100
Bluher, M; Krohn, K; Wallaschofski, H et al. (1999) Fas and Fas ligand gene expression in autoimmune thyroiditis in BB/W rats. Eur J Endocrinol 141:506-11
Lawrence, J E; Lamm, S H; Braverman, L E (1999) The use of perchlorate for the prevention of thyrotoxicosis in patients given iodine rich contrast agents. J Endocrinol Invest 22:405-7
Mori, K; Stone, S; Khaodhiar, L et al. (1999) Induction of transcription factor interferon regulatory factor-1 by interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha) in FRTL-5 cells. J Cell Biochem 74:211-9
Colzani, R M; Alex, S; Fang, S L et al. (1999) Effects of iodine repletion on thyroid morphology in iodine and/or selenium deficient rat term fetuses, pups and mothers. Biochimie 81:485-91
Bluher, M; Krohn, K; Wallaschofski, H et al. (1999) Cytokine gene expression in autoimmune thyroiditis in BioBreeding/Worcester rats. Thyroid 9:1049-55

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