Regulation of thyroxine 5'-deiodinase by thyroid hormones and activators of protein kinase C in GH4C1 cells.
The regulation of T4 5'-deiodinase activity was studied in cultured GH4C1 cells. Enzyme activity was measured in cell sonicates as the release of radioiodide from [125I]T4. Enzyme activity was stimulated 2- to 3-fold by hypothyroid serum and activators of protein kinase C, such as TRH and phorbol esters. The hypothyroid serum effect was maximal by 3 h, whereas TRH and phorbol esters required 6 h to achieve a maximal effect. The hypothyroid serum effect was gone within 4 h of returning the cells to control medium. In contrast, the TRH and phorbol ester effects persisted 24-48 h after removal of those agents. Both T4 and rT3 were at least as potent as T3 in blocking the effect of hypothyroid serum. The stimulation of 5'-deiodinase induced by hypothyroid serum was additive with that induced by kinase C activators. Trifluoperazine blocked the effect of TRH and phorbol esters, but not that of hypothyroid serum. It is concluded that stimulation of 5'-deiodinase activity can occur by at least two independent mechanisms: one involving hypothyroidism and another involving activation of protein kinase C. The relative potencies of various iodothyronines for abolishing the hypothyroid effect differ markedly from the relative binding affinities of these agents for the nuclear T3 receptor, suggesting that this thyroid hormone effect may not be mediated by the classical nuclear thyroid hormone receptor.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D007037:Hypothyroidism / Q000201:enzymology; D007453:Iodide Peroxidase / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D010911:Pituitary Neoplasms / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013963:Thyroid Hormones / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D013974:Thyroxine / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology; D014285:Triiodothyronine, Reverse / Q000494:pharmacology
D010703:Phorbol Esters; D013963:Thyroid Hormones; D014284:Triiodothyronine; D005576:Colforsin; D014268:Trifluoperazine; D015124:8-Bromo Cyclic Adenosine Monophosphate; C008876:phorbol-12,13-didecanoate; C016276:8-bromocyclic GMP; D000001:Calcimycin; D014285:Triiodothyronine, Reverse; D013973:Thyrotropin-Releasing Hormone; D007453:Iodide Peroxidase; D011493:Protein Kinase C; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate; D013974:Thyroxine