Structure and function of the TSH receptor: Its suitability as a target for radiotherapy

Systemic radiotherapy, such as radioimmunotherapy, is an exciting and rapidly growing field of medical therapeutics for a variety of solid and diffuse human malignancies. This therapy involves the systemic administration of a radionuclide, attached to a carrier ligand (such as a hormone analogue or monoclonal antibody), which becomes directed at the tumor through a target receptor or antigen that resides within the malignant tissue. The thyrotropin receptor (TSHr) is a membrane-bound glycoprotein through which the pituitary communicates with thyroid follicular cells. Because it is a thyroid-specific protein and is expressed frequently in differentiated thyroid cancers, it is a potential candidate target for systemic radiotherapy of these malignancies. I will examine the general structure of TSHr and its potential utility as such a target. Several obstacles regarding the concentration and distribution of TSHr as well as the availability of a suitable carrier ligand must be overcome before radioimmunotherapy of thyroid cancers using TSHr as target becomes a reality.