[Structure-function relationship of glycoprotein hormone].

Abstract

Thyroid-stimulating hormone (TSH) is a member of a family of heterodimeric glycoprotein hormones which have a common alpha-subunit but differ in their hormone-specific beta-subunit. To date, numerous studies have been carried out to elucidate the structure-function relationship of glycoprotein hormones and molecular mechanism of hormone action. On the other hand, several types of abnormality in the structure and function of glycoprotein hormones, as well as TSH, have been observed in clinical samples, especially in malignant diseases. To approach the structure-function relationships of bioactive molecules, monoclonal antibodies have proven to be excellent tools. In the present study, on the basis of epitope analysis using 19 different monoclonal antibodies against human TSH, the surface structure of this hormone was proposed in a two-dimensional map. The epitope map of TSH was useful for construction of available immunoassays for this hormone and its subunit, and to detect the abnormality in the structure of recombinant TSH. Further studies were attempted to assess the effects of monoclonal antibodies on the function of TSH. Consequently, our results suggest that the beta-subunit is indispensable for recognizing the receptor and that the alpha-subunit is required for signal transduction in postreceptor step(s). The applications of the present analysis are underway to detect the abnormalities in the structure and function of TSH in clinical specimens.