THE DISTINCT ROLES OF ALPHA-SUBUNITS AND BETA-SUBUNITS OF HUMAN THYROTROPIN IN THE RECEPTOR-BINDING AND POSTRECEPTOR EVENTS

The roles of α- and β-subunits of human TSH (hTSH) were studied by investigating the inhibitory effects of monoclonal antibodies on the biological activity of hTSH. Four monoclonal antibodies directed toward different epitopes on the β-subunit (hTSHβ) inhibited completely the receptor binding of hTSH to FRTL-5 rat thyroid cells. In contrast, five monoclonal antibodies directed toward different epitopes on the α-subunit had little or no effect on the receptor binding. Furthermore, four of five α-subunit-specific antibodies and three of four hTSH- specific antibodies inhibited both hTSH-induced cAMP accu-mulation and thymidine uptake in FRTL-5 cells, in a dose- response manner. One hTSH (α-β heterodimer)-specific antibody which did not recognize the free subunits also had the inhibitory effect on both the receptor binding and hTSH-induced cAMP accumulation. These results strongly suggest that hTSHβ is indispensable for recognizing the receptors on FRTL-5 cells and that the α- subunit is required for signal transduction in postreceptor step(s). In addition, it is also suggested that the highly confor-mational structure of hTSH is absolutely essential for the bio-logical activity. © 1990 by The Endocrine Society.