Structure-function relationships in the mechanisms by which glycoprotein hormones (thyrotropin), autoantibodies, alpha I- adrenergic agents, insulin, insulin-like growth factors (I and II). bacterial toxins (cholera and pertussis, for examples, the anti- viral protective agent, interferon, and interleukins - alone and in combination - interact with and transmit their message through the cell membrane to affect cell function and pathology are being defined. Studies using monoclonal antibodies and the idiotype antiidiotype theory explore the structure of the receptors for these ligands and the importance of these relationships to the expression of thyroid hyperfunction in Graves' diseases; to organ- specific autoimmunity (Graves' disease, Hashimoto's disease, and diabetes); to fluid losses in intestinal diarrheic states; to thyroid storm and the sympathetic overactivity syndrome of tetanus; to the ability of hormones to modulate the oncogenic states and to the mechanism by which toxins subvert normal mechanisms to impose their pathological effects. Studies continue to evaluate the role of different signal transduction mechanisms - cAMP, Ca/phosphoinositide and arachidonate - by these agents for growth and differentiation for example, thyroglobulin biosynthesis, thyroglobulin biodegradation to T3 and T4, and the transport of T3, T4, monoiodotyrosine, diiodotyrosine, and other amino acids from the lysosome. The role of phosphate and carbohydrate moieties in thyroglobulin structure and posttranslational processing is being studied. Studies explore lipid regulation of receptor expression. with special emphasis or neuronal and thyroid cell growth and development as well as the hormonal regulation of lipid metabolism, LDL receptor expression, and cholesterol biosynthesis. Studies to clone the TSH receptor and define its structure and regulatory control at a gene level are In progress as are studies to define the mechanisms by which TSH, insulin, IGF-I and other ligands regulate gene expression.
