ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: 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 10−7M 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 (10−3M) 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). Platelet-derived growth factor (20 ng/ml) and epidermal growth factor (100 ng/ml) were poor inducers of 5-D activity (8- to 12-fold increase at 8 h); insulin (10−6M) was without effect. The 5-D activity induced by TPA and acidic fibroblast growth factor manifested the characteristics of type III 5-D (Km for T3 0.5–0.8 nM, thiol-dependent, 6-n-propyl-2-thiouracil-insensitive). The results demonstrate that, like 5′-D activity, 5-D activity is induced by multiple pathways. The relative potencies of TPA, fibroblast growth factors, and cyclic AMP on 5-D and 5′-D activities were different, as were the time courses of their actions. These data indicate that 5- and 5′-D are distinct enzymes and support the view that T3 availability may be controlled not only by regulating T3 production, but also by regulating T3 and T4 degradation.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1991.tb11399.x
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