Abstract

This is a proposal to carry forward studies of diverse aspects of thyroid hormone economy as they relate to the normal ohysiology of the thyroid andits hormones in man and animals andto the pathogenesis and psthophysiology of thyroid diseases. Studies are planned in four major area of investigation: 1) the peripheral metabolism of thyroid hormones; 2) the mechanism of action of thyroid hormones; 3) regulation of thyroid cell grwoth; and 4) the pathogenesis and pathophysiology of Graves' disease and other autoimmune diseases. Studies of thyroid hormone metabolism will concentrate on a newly-documented pathway of hormone metabolism, cleavage of the other link of the iodothyronine molecule, and will be directed toward quantitating its activity in man and in rats and determing the factors that influence its activity. Studies of the mechanism of action of thyroid hormones will concentrate on those mediated at the plasma membrane and will attempt to determine whether effects of this nature observed in thymic lymphocytes reflect a general and similar response in bodily tissues. Studies of the factors that influence thyroid cell growth will, in part, extend observations concerning the effects of tissue growth factors on the growth and function of thyroid cells in culture and will seek to elucidate their mechanism of action. In addition, the contribution of antibodies that stimulate or inhibit thyroid growth to the pathogenesis of various thyroid diseases will be evaluated and their interaction with tissue growth factors will be explored. Studies of the pathogenesis of Graves' disease have several objectives: to establish an animal model of Graves' disease by immunizing them with unique antigens, including bacter-extracts, that contain TSH receptors; to explore the relationship of other bacterial antigens to the pathogenesis of other thyroid diseases, to elucidate the effects of various lymphokines on the thyroid follicular cell and to explore their interaction with growth factors and antibodies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK018416-15
Application #
3226029
Study Section
Endocrinology Study Section (END)
Project Start
1975-10-01
Project End
1991-02-28
Budget Start
1989-03-01
Budget End
1990-02-28
Support Year
15
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Rosen, H N; Murrell, J R; Liepnieks, J J et al. (1994) Threonine for alanine substitution at position 109 of transthyretin differentially alters human transthyretin's affinity for iodothyronines. Endocrinology 134:27-34
Cissewski, K; Faix, J D; Reinwein, D et al. (1993) Factitious hyperthyroxinemia due to a monoclonal IgA in a case of multiple myeloma. Clin Chem 39:1739-42
Rosen, H N; Moses, A C; Murrell, J R et al. (1993) Thyroxine interactions with transthyretin: a comparison of 10 different naturally occurring human transthyretin variants. J Clin Endocrinol Metab 77:370-4
Murrell, J R; Schoner, R G; Liepnieks, J J et al. (1992) Production and functional analysis of normal and variant recombinant human transthyretin proteins. J Biol Chem 267:16595-600
Akiguchi, I; Strauss, K; Borges, M et al. (1992) Thyroid hormone receptors and 3,5,3'-triiodothyronine biological effects in FRTL5 thyroid follicular cells. Endocrinology 131:1279-87
Cissewski, K; Wolf, M; Moses, A C (1992) Characterization of insulin-like growth factor receptors in human thyroid tissue. Receptor 2:145-53
Wolf, M W; Misaki, T; Bech, K et al. (1991) Immunoglobulins of patients recovering from Yersinia enterocolitica infections exhibit Graves' disease-like activity in human thyroid membranes. Thyroid 1:315-20
Hintze, G; Braverman, L E; Ingbar, S H (1991) The effect of surgical stress on the in vitro metabolism of thyroxine by rat liver, kidney, and brain. Endocrinology 128:146-52
Nomura, T; Borges, M; Ingbar, S H et al. (1990) Factors determining the differential tissue response of Na/K-ATPase to thyroid hormone in the neonatal rat. Metabolism 39:1049-55
Silva, J E; Rudas, P (1990) Effects of congenital hypothyroidism on microtubule-associated protein-2 expression in the cerebellum of the rat. Endocrinology 126:1276-82

Showing the most recent 10 out of 15 publications