On the mechanism of 'escape' from desensitization of the cyclic AMP response to TSH in cultured human thyroid cells.
Studies were conducted to examine the mechanism by which 'escape' from TSH desensitization of the cyclic AMP response to TSH (Endocrinology 109, 1156, 1981) occurs in confluent cultured thyroid cells. At confluence, cell replication and DNA synthesis are suppressed. An attempt was therefore made to reproduce escape in sparse thyroid cell monolayers using inhibitors of DNA synthesis. The concurrent presence of TSH and mitomycin C (5 micrograms/ml) did not influence the induction of desensitization to TSH after 6 h of stimulation, but cAMP levels then rebounded by 24 h; that is, mitomycin C reproduced escape in sparse cells. Hydroxyurea (10 mM) did not reproduce escape in sparse cells. Adenylate cyclase activity was unaltered in plasma membranes prepared from sparse thyroid cells treated with mitomycin C for 24 h. These data suggest that 'escape' from TSH desensitization is related to events occurring during the cell cycle associated with DNA synthesis, and is caused by an alteration in adenylate cyclase substrate or co-factor availability rather than in enzyme activity itself.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects; D004351:Drug Resistance; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects; D013972:Thyrotropin / Q000494:pharmacology*; D013997:Time Factors
D008937:Mitomycins; D016685:Mitomycin; D013972:Thyrotropin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine; D006918:Hydroxyurea