THYROTROPIN-DEPENDENT DESENSITIZATION BY CHINESE-HAMSTER OVARY CELLS THAT EXPRESS THE RECOMBINANT HUMAN THYROTROPIN RECEPTOR

To determine whether thyrotrophin (TSH)-induced desensitization requires a thyroid-specific factor(s), the human TSH (hTSH) receptor was expressed in Chinese hamster ovary cells. The first incubation of the cells with TSH decreased the subsequent response of adenosine 3',5'-cyclic monophosphate to freshly added TSH in the second incubation. This homologous desensitization was observed as early as after 3 h of the first incubation. The lowest dose of TSH that elicited desensitization was 0.1 nmol/l. The desensitization was not overcome by adding higher doses of TSH in the second incubation. A I-125-labelled TSH-binding study revealed a decrease in the number of high-affinity binding sites but not in that of low-affinity binding sites. The data suggest that TSH-induced desensitization in hTSH receptor-transfected cells is caused, at least in part, by a decrease in the number of TSH receptors on the cell surface. The evidence demonstrates, contrary to an earlier report, that a thyroid-specific factor(s) is not required for hTSH receptor desensitization.