Human TSH receptor ligands as pharmacological probes with potential clinical application

Abstract

The biologic role of thyroid-stimulating hormone (TSH; thyrotropin) as an activator (agonist) of the TSH receptor (TSHR) in the hypothalamic–pituitary–thyroid axis is well known and activation of TSHR by recombinant human TSH is used clinically in patients with thyroid cancer. TSHR ligands other than TSH could be used to probe TSHR biology in thyroidal and extrathyroidal tissues, and potentially be employed in patients. A number of different TSHR ligands have been reported, including TSH analogs, antibodies and small-molecule, drug-like compounds. In this review, we will provide an update on all these classes of TSHR agonists and antagonists but place emphasis on small-molecule ligands.

Keywords::

• small molecule
• thyroid-stimulating hormone
• thyrotropin
• TSH analogs
• TSHR antagonists
• TSHR agonists
• TSHR antibodies
• TSH receptor
• TSHR ligands

Acknowledgements

The authors thank all of their collaborators who have contributed to the TSHR small-molecule research.

Financial & competing interests disclosure

The authors’ research was supported by the Intramural Research Program, NIDDK, NIH (1 Z01 DK011006 CEB and 1 Z01 DK 047044 CEB). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.