Induction of 5-deiodinase activity in astroglial cells by 12-O-tetradecanoylphorbol 13-acetate and fibroblast growth factors.
In the brain, 5'-deiodinase (5'-D) is responsible for the metabolic activation of thyroxine (T4) into 3,5,3'-triiodothyronine (T3) and 5-deiodinase (5-D) deiodinates T4 and T3 into inactive metabolites. This study examines the effects of factors known to induce astroglial 5'-D activity on the 5-D activity in cultured rat astroglial cells. The potencies of these factors were compared after 8 h of incubation, when stimulations by these factors near their maximal effects. 12-O-Tetradecanoylphorbol 13-acetate (TPA) at 10(-7) M was a potent inducer of 5-D activity, producing a 30- to 80-fold increase after 8 h. The maximal effect of TPA was observed after about 14 h. The TPA stimulation of 5-D activity was not dependent on glucocorticoids, unlike 5'-D activity. In comparison with TPA, 8-bromo-cyclic AMP (10(-3) M) was a poor inducer of 5-D activity whereas it is an excellent inducer of 5'-D activity. It produced a 2- to 20-fold increase in 5-D activity after 8 h. Natural acidic fibroblast growth factor (20 ng/ml) produced a degree of stimulation similar to that of TPA after 8 h. The maximal effect of acidic fibroblast growth factor was observed after about 16 h (until a 120-fold increase). Recombinant acidic fibroblast growth factor also induced 5-D activity. Basic fibroblast growth factor was less potent than acidic fibroblast growth factor for increasing 5-D activity (maximal increase by 40- to 50-fold after 8 h).(ABSTRACT TRUNCATED AT 250 WORDS)
Courtin
F
F
U. 96 INSERM, Unité de Recherche sur la Glande Thyroïde et la Régulation Hormonale, Le Kremlin-Bicêtre, France.
Liva
P
P
Gavaret
J M
JM
Toru-Delbauffe
D
D
Pierre
M
M
D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D005346:Fibroblast Growth Factors; D006493:Heparin; D007453:Iodide Peroxidase; D013755:Tetradecanoylphorbol Acetate