TRIIODOTHYRONINE RECEPTORS AND NONTHYROIDAL DISEASES

Project: Research project

Project Details

Description

We will continue to study the rat bearing the transplantable Walker 256
carcinoma (T) with decreased serum T4 and T3 but normal TSH as a model for
patients with nonthyroidal disease who have decreased serum T3. We propose
to determine whether the previously described decrease in hepatic nuclear
T3 receptors reflects a specific or general change in nonhistone protein
synthesis, whether other aspects of hepatic protein synthesis are altered
in T rats and whether anterior pituitary nuclear T3 receptor and GH content
are changed in these animals. We will characterize the dose-response curve
for pituitary GH content in relation to the saturation of pituitary nuclear
receptors. Hepatic nuclear T3 receptor forms will be characterized by
means of a T3 photoaffinity probe and the t 1/2 of receptor will be
determined. The response of the thyroid to endogenous TSH will also be
measured. Additional studies will examine the influence of nonthyroidal
disease on experimental thyrotoxicosis. Walker 256 carcinoma and
experimental laparotomy will be used in rats with acute and chronic
experimental thyrotoxicosis. Biological responses to T3 such as
hepatic-glycerophosphate dehydrogenase and malic enzyme activity and
pituitary GH content will be assessed. We propose to study further tumor products in serum from T rats and
conditioned medium from cultured cloned Walker 256 carcinoma which decrease
nuclear T3 receptor levels in cultured GC cells. Tumor product effects on
receptor synthesis and turnover in GC cells, on receptor synthesis in
relation to GC cell nonhistone protein synthesis, and on T3 action
(receptor depletion, GH induction, growth, amino acid transport will be
examined. Lastly, we will continue to study the interaction between
5,5'-diphenylhydantoin (DPH) and the thyroid hormone system. We will
explore the possible use of DPH in experimental thyrotoxicosis and we will
test the effect of DPH on the rate of growth and GH production of GC cell
tumors transplanted subcutaneously in rats.
StatusFinished
Effective start/end date7/1/826/30/91

Funding

  • National Institutes of Health

ASJC

  • Medicine(all)
  • Endocrine and Autonomic Systems
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Pharmacology

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