IN CHINESE-HAMSTER OVARY K1 CELLS DOG AND HUMAN THYROTROPIN RECEPTORSACTIVATE BOTH THE CYCLIC-AMP AND THE PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE CASCADES IN THE PRESENCE OF THYROTROPIN AND THE CYCLIC-AMP CASCADE IN ITS ABSENCE

Thyrotropic hormone, through its human thyrotropin receptor, activates both the cyclic AMP and the phosphatidylinositol 4,5-bisphosphate-pho spholipase-C cascades in human thyroid cells and in Chinese hamster ov ary cells (CHO-K1) expressing this receptor. However, thyrotropin only activates the cyclic-AMP cascade in dog thyroid cells. In order to es tablish whether this different pattern of responses reflects a differe nt structure of the human and dog thyrotropin receptors, CHO-K1 cells were permanently transfected with a plasmid coding for one or the othe r receptor. For various levels of receptor expression, CHO-K1 cells ex pressing either receptor presented qualitatively similar cyclic AMP an d inositol phosphates responses to thyrotropin. This suggests that the difference in the response of the dog and human thyroid to thyrotropi n involves elements of the phosphatidylinositol 4,5-bisphosphate casca de downstream of the receptor. In CHO-K1 cells overexpressing the thyr otropin receptor, the basal level of cyclic AMP was raised, suggesting a constitutive activity of the wild-type receptor. This was confirmed in COS-7 cells transiently expressing the human or dog thyrotropin re ceptors, the basal cyclic AMP levels of these cells increased in paral lel with thyrotropin binding. This spontaneous activity of the thyrotr opin receptor may have physiological and pathological consequences.