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Thyroid hormone regulation of thyrotropin gene expression
W W Chin1, F E Carr, J Burnside
1Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Recent Progress in Hormone Research
|January 1, 1993
Summary
Thyroid hormones regulate TSH gene expression via transcriptional mechanisms. Researchers identified specific DNA sequences (TREs) in the TSH subunit gene promoters critical for this negative feedback loop.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Thyroid hormones are crucial for regulating metabolism through the pituitary-thyroid axis.
- Negative feedback by thyroid hormones on thyrotropin (TSH) synthesis is essential for endocrine homeostasis.
- Thyroid hormone action primarily occurs at the transcriptional level, influencing gene expression.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying thyroid hormone's negative regulation of TSH subunit gene expression.
- To identify and characterize the specific DNA sequences (thyroid hormone response elements - TREs) involved in this regulation.
- To explore the roles of different thyroid hormone receptor (TR) isoforms and co-factors in mediating thyroid hormone's effects.
Main Methods:
- Isolation and characterization of TSH subunit genes.
- Structure-function analyses using fusion genes.
- DNA transfection assays in relevant cell models.
- Sequence analysis of gene promoters across species (rat, mouse, human).
Main Results:
- Defined specific negative thyroid hormone response elements (TREs) within the alpha and TSH beta gene promoters.
- Identified distinct TRE arrangements (overlapping half-sites, gapped repeats, single half-sites) different from positive TREs.
- Highlighted the involvement of multiple TR isoforms and TRAP heterodimer partners in negative regulation.
Conclusions:
- Thyroid hormone exerts negative feedback on TSH gene expression primarily through transcriptional mechanisms.
- Specific DNA sequences and their arrangements in TSH subunit gene promoters mediate this regulation.
- Further research is needed to fully understand the complex interplay of TRs, co-factors, and thyroid hormones in gene regulation, including post-transcriptional effects.