Reverse T3 and modulators of the calcium messenger system rapidly decrease T4-5'-deiodinase II activity in cultured mouse neuroblastoma cells.
Neural T3 neogenesis is modulated by the enzyme T4-5'-deiodinase type II (T4-5'-DII). Hypothyroidism increases the activity of rat pituitary and cerebral cortex enzyme activity. Mouse neuroblastoma cells (NB41A3) incubated in thyroid hormone deficient medium also show a significant increase in T4-5'-DII activity. This response is rapidly (less than 30 minutes) reversed by reverse T3 (rT3) suggesting a mechanism independent of nuclear T3 receptor binding or new protein synthesis. This report details a series of studies performed to elucidate the nature of this rT3 effect. Confluent neuroblastoma cell culture preparations maintained in hypothyroid medium showed a 2-3 fold increase in T4-5'-DII activity compared to preparations in standard medium (p less than 0.001). RT3 (1-50 nM), the calcium ionophore A23187 (0.3-1.5 microM) and the phorbol ester TPA (0.1-1.0 microM) reversed the effect of thyroid hormone deficient medium on enzyme activity (p less than 0.001). Each agent showed a similar time course with maximal effect occurring between 15-30 minutes post medium supplementation. The suppressive effect of A23187 (1.5 microM) and TPA (0.5 microM) on enzyme activity was not additive. In addition, the combination o of rT3 (50 nM) and A23187 (1.5 nM) did not decrease enzyme activity compared to each agent alone. In contrast, the combined addition of rT3 (50 nM) and TPA (0.5 microM) did have an additive effect on neuroblastoma T4-5'-DII activity. A similar pattern of response was found, when the effects of these agents were analyzed on T4-5'-DII activity in neuroblastoma cells incubated in N-FSC.(ABSTRACT TRUNCATED AT 250 WORDS)
Gavin
L A
LA
Division Endocrinology-Metabolism, Veterans Administration Medical Center, San Francisco, CA 94121.
Moeller
M
M
Shoback
D
D
Cavalieri
R R
RR
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000378:metabolism*; D051379:Mice; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D014285:Triiodothyronine, Reverse / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000378:metabolism
D014285:Triiodothyronine, Reverse; D007453:Iodide Peroxidase; D011493:Protein Kinase C; D002118:Calcium