title: In vitro regulation of ornithine decarboxylase in dog thyroid slices.
abstract: Ornithine decarboxylase (ODC) activity in dog thyroid slices incubated in vitro disappears when protein or RNA synthesis is inhibited. Thus, as in other tissues, the level of the enzyme reflects a balance between rapid synthesis and catabolism. TSH, dibutyryl cAMP, prostaglandin E1 (PGE1), and cholera toxin all stimulated dog thyroid ODC activity. These actions were potentiated by the inhibitor of phosphodiesterases, 4-(3-butoxy-4-methoxy-benzyl)2-imidazolidinone (Ro 20-1724), and reproduced by high concentrations of this inhibitor, while 1-methyl-3-isobutylxanthine inhibited ODC induction. Iodide blocked the action of TSH; this inhibition was relieved by methimazole. Calcium depletion or manganese addition depressed enzyme levels in control and stimulated tissue. In some cases (ionophore A23187 addition and calcium depletion), total protein synthesis was also depressed. Carbamylcholine and the ionophore A23187, which can raise cGMP in thyroid slices, inhibited TSH and dibutyryl cAMP induced ODC increases, PGF1 alpha was inhibitory to ODC stimulation. Indomethacin, which had no effect on TSH action, relieved carbamylcholine inhibition. These results show that dog thyroid ODC is stimulated by TSH through cAMP, and suggest that cholinergic stimulation of the tissue blocks TSH activation of the enzyme, possibly at a step beyond cAMP synthesis, by increasing PGF synthesis. The effect of carbamylcholine is not due to cGMP, since it can be obtained under conditions where basal cGMP levels are not increased.
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002262:Carboxy-Lyases / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004285:Dogs; D066298:In Vitro Techniques; D007700:Kinetics; D008345:Manganese / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000096:biosynthesis / Q000378:metabolism*; D011460:Prostaglandins F / Q000494:pharmacology; D011691:Puromycin / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects / Q000201:enzymology*; D013972:Thyrotropin / Q000494:pharmacology
chemical_list: D011460:Prostaglandins F; D003609:Dactinomycin; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D008345:Manganese; D011691:Puromycin; D013972:Thyrotropin; D003513:Cycloheximide; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine