Sustained versus transient cyclic AMP intracellular levels: effect on thyrotropin-dependent growth of thyroid cells.
Cyclic AMP (cAMP) is the second messenger that stimulates growth and differentiation of thyroid cells, which are dependent upon thyrotropin for the initiation of the cell cycle. Treatment of thyroid cells with phosphodiesterase inhibitors, such as 1-methyl-3-isobutylxanthine (IBMX), RO-20-1724, or aminophylline, induces persistent levels of cAMP and blocks cell proliferation. IBMX-treated cells are arrested at the G1-S border, but removal of the drug allows cell growth to resume. The inhibiting effect of IBMX is dose dependent, and the phase of the cell cycle is irrelevant. These data indicate that prolonged and steady accumulation of cAMP blocks the cell cycle in thyroid cells.
Villone
G
G
Dipartimento di Medicina Sperimentale e Clinica, Università di Reggio Calabria, Catanzaro, Italy.
De Amicis
F
F
Veneziani
B M
BM
Salzano
S
S
Di Carlo
A
A
Tramontano
D
D
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D018398:Homeodomain Proteins / Q000096:biosynthesis; D007454:Iodides / Q000493:pharmacokinetics; D009687:Nuclear Proteins / Q000096:biosynthesis; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D015290:Second Messenger Systems; D013961:Thyroid Gland / Q000166:cytology*; D000074482:Thyroid Nuclear Factor 1; D013972:Thyrotropin / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis
D018398:Homeodomain Proteins; D007454:Iodides; D009687:Nuclear Proteins; D010726:Phosphodiesterase Inhibitors; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D013972:Thyrotropin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015056:1-Methyl-3-isobutylxanthine