The G2M arrest caused by iodide is unrelated to the effects of iodide at adenylate cyclase.
Previously, we have shown that the iodide was able to inhibit TSH induced thyrocyte proliferation by arresting the cell cycle at G0G1 and G2M, suggesting that the iodide may be exerting its effects through more than the TSH-adenylate cyclase-cAMP system. To confirm the effects of iodide on the adenylate cyclase (AC) system, forskolin- and dibutyryl-cyclic-AMP (dBcAMP)-stimulated FRTL5 thyroid cells were exposed to inhibitory concentrations of iodide and the resultant effects on the cell cycle were compared to the effects observed with TSH, using flow cytometric DNA analysis. Forskolin stimulated the proliferation of FRTL5 cells in a dose-dependent manner. Cell numbers rose from baseline by 169 +/- 4% to peak at 10 microM forskolin. Interestingly, 100 microM forskolin inhibited cell proliferation, causing cell numbers to fall by approximately 50%. Iodide inhibited forskolin-induced proliferation to baseline levels. However, the pattern of cell cycle perturbation was different to that with TSH-stimulated cells. There were no differences in the proportion of cells in G0G1 between forskolin alone and forskolin + NaI, while there was a marked fall in the proportion of cells in S phase, indicating possible partial arrest at G0G1. Furthermore, there was a marked accumulation of cells in G2M over and above that found with TSH + NaI, indicating arrest at G2M. dBcAMP maximally stimulated cell numbers to rise from baseline by 125% with 1 mM dBcAMP. Again, higher concentrations of the mitogen had an inhibitory effect on proliferation. The addition of NaI inhibited dBcAMP stimulated cell proliferation.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects*; D007454:Iodides / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects*; D051381:Rats; D013972:Thyrotropin / Q000494:pharmacology
D007454:Iodides; D005576:Colforsin; D003994:Bucladesine; D013972:Thyrotropin; D000262:Adenylyl Cyclases