title: Lack of relationship between 3',5'cyclic adenosine monophosphate desensitization and thyrotropin receptor down regulation in the rat thyroid cell line FRTL5.
abstract: 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 125I-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 microU/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.
authors.affiliation: Cattedra di Endocrinologia, Università di Catania, Ospedale Garibaldi, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Foti
authors.forename: R
authors.initials: R
authors.lastname: Catalfamo
authors.forename: D
authors.initials: D
authors.lastname: Russo
authors.forename: G
authors.initials: G
authors.lastname: Costante
authors.forename: S
authors.initials: S
authors.lastname: Filetti
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D007700:Kinetics; D051381:Rats; D011989:Receptors, Thyrotropin / Q000378:metabolism*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D011989:Receptors, Thyrotropin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D013972:Thyrotropin; D000242:Cyclic AMP