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Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships.
Mariusz W Szkudlinski1, Valerie Fremont, Catherine Ronin
1Section of Protein Engineering, Laboratory of Molecular Endocrinology, Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Maryland, USA. mszkudlinski@trophogen.com
Physiological Reviews
|March 28, 2002
Summary
Recent advances in thyroid-stimulating hormone (TSH) and TSH receptor (TSHR) structure-function relationships enhance understanding of hormone synthesis, bioactivity, and activation mechanisms. This knowledge aids in developing novel TSH analogs for therapeutic applications.
Area of Science:
- Endocrinology
- Molecular Biology
- Structural Biology
Background:
- Thyroid-stimulating hormone (TSH) regulates thyroid function via its receptor (TSHR), a G protein-coupled receptor (GPCR).
- Understanding TSH-TSHR interactions is crucial for thyroid physiology and disease pathogenesis.
Purpose of the Study:
- To review recent advances in TSH and TSHR structure-function relationships.
- To integrate current knowledge on TSH bioactivity, receptor activation, and therapeutic analog development.
Main Methods:
- Site-directed mutagenesis
- Peptide and antibody approaches
- Sequence analysis
- Molecular modeling
- Analysis of naturally occurring mutations
Main Results:
- New insights into TSH domains governing receptor recognition, synthesis, bioactivity, and clearance.
- Elucidation of molecular mechanisms underlying TSHR activation, including constitutive activity.
- Understanding the evolution of TSH bioactivity and development of high-affinity TSH analogs.
Conclusions:
- Advances in TSH-TSHR structure-function studies offer significant structural, physiological, and therapeutic implications.
- This knowledge is relevant to understanding GPCR activation and developing novel therapeutics, with parallels to gonadotropin research.