LACK OF RELATIONSHIP BETWEEN 3', 5'CYCLIC ADENOSINE-MONOPHOSPHATE DESENSITIZATION AND THYROTROPIN RECEPTOR DOWN REGULATION IN THE RAT-THYROID CELL-LINE FRTL5

We studied the cAMP response and radioiodinated TSH binding in the FRTL5 rat thyroid cell line after chronic exposure to TSH. In parallel experiments, continuous exposure to TSH induced both a decrease in the cellular cAMP responsiveness to a second acute stimulation by thyrotropin (desensitization) and a reduction in I-125-TSH cellular binding (down-regulation). These two processes appeared to differ in that: a) cAMP desensitization was maximal (45-55% inhibition in comparison to control cells) after 24 h of preexposure to TSH; on the contrary, a loss of the TSH binding to thyroid cells was detected only after 24 h and was maximal (55-65% lower than control cells) after 48 h of preexposure to TSH; b) a different dependence on the TSH dose was observed for cAMP desensitization and TSH down-regulation: the former was maximal at 10-mu-U/ml of TSH, the latter only at 10 mU/ml of TSH; c) recovery from cAMP desensitization was detected 3 h after TSH withdrawal and was fully achieved at 24 h, whereas the recovery from the TSH receptor down-regulation was not evident for up to 24 h and a full recovery obtained only at 72 h; d) the use of cAMP analogues proved that, unlike desensitization, TSH receptor down-regulation is a cAMP dependent process. These findings support the concept that different patterns of response to prolonged stimulation with TSH, an earlier and cAMP-independent process (desensitization) and a later cAMP-dependent mechanism (down-regulation), occur in the rat thyroid cell.