Abstract

We will study the mechanism through which thyroid hormone controls transcription and mRNA levels for specific genes. Nuclear receptors for thyroid hormone will be purified by column chromatography, by development of antibodies to the receptor by binding to specific DNA sequences. We will attempt to clone the receptor gene by using an expression vector system. A group of cloned thyroid hormone responsive genes will be assembled, and we will determine the DNA sequences, within the genes and flanking elements, to which thyroid hormone receptor binds. These studies will utilize DNA cellulose binding, methylation, and footprinting techniques. We will purify a nuclear protein induced by thyroid hormone treatment, and clone the gene for this protein. The effect of T3 on processing and stabilization of heterogenous nuclear RNA for specific genes will be studied using in vivo and in vitro systems. Receptor function will be studied in cultured fibroblasts from normal subjects and patients with thyroid hormone resistance.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK013377-20
Application #
3225039
Study Section
Endocrinology Study Section (END)
Project Start
1976-05-01
Project End
1989-02-28
Budget Start
1987-12-01
Budget End
1989-02-28
Support Year
20
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Chicago
Department
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637

  Publications

Takeda, T; Nagasawa, T; Miyamoto, T et al. (1997) The function of retinoid X receptors on negative thyroid hormone response elements. Mol Cell Endocrinol 128:85-96
Liu, R T; Suzuki, S; Takeda, T et al. (1996) An artificial thyroid hormone receptor mutant without DNA binding can have dominant negative effect. Mol Cell Endocrinol 120:85-93
Ozata, M; Suzuki, S; Takeda, T et al. (1995) Functional analysis of a proline to serine mutation in codon 453 of the thyroid hormone receptor beta 1 gene. J Clin Endocrinol Metab 80:3239-45
Takeda, T; Suzuki, S; Liu, R T et al. (1995) Triiodothyroacetic acid has unique potential for therapy of resistance to thyroid hormone. J Clin Endocrinol Metab 80:2033-40
Liu, R T; Suzuki, S; Miyamoto, T et al. (1995) The dominant negative effect of thyroid hormone receptor splicing variant alpha 2 does not require binding to a thyroid response element. Mol Endocrinol 9:86-95
DeGroot, L J; Gorman, C A; Pinchera, A et al. (1995) Therapeutic controversies. Retro-orbital radiation and radioactive iodide ablation of the thyroid may be good for Graves' ophthalmopathy. J Clin Endocrinol Metab 80:339-40
Fierro-Renoy, J F; Szuchet, S; Falcone, M et al. (1995) Three different thyroid hormone receptor isoforms are detected in a pure culture of ovine oligodendrocytes. Glia 14:322-8
Okamoto, Y; Hayashi, Y; DeGroot, L J (1995) Expression of human thyrotropin receptor by recombinant adenovirus. Thyroid 5:51-3
Sakurai, A; Suzuki, S; Katai, M et al. (1995) Transcriptional regulation of human thyroid hormone receptor beta 1 gene expression: effect of human retinoid X receptor and identification of a transcriptional silencer region. Mol Cell Endocrinol 110:103-12
Suzuki, S; Takeda, T; Liu, R T et al. (1995) Importance of the most proximal GC box for activity of the promoter of human thyroid hormone receptor beta 1. Mol Endocrinol 9:1288-96

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