Induction of type III deiodinase activity in astroglial cells by thyroid hormones.
The type III deiodinase (D-III) activity in astroglial cells is induced by multiple pathways activated by cAMP, 12-O-tetradecanoylphorbol-13-acetate (TPA), and fibroblast growth factors (FGFs). This study examines the effects of thyroid hormones on D-III activity in astroglial cells with or without induction by these factors. Addition of 10 nM T3 to the culture medium caused a slow increase in D-III activity, which reached a plateau after 48 h. This increase was concentration dependent (maximal response at 10 nM). Doses as low as 0.3 nM caused significant increases in D-III activity. The effect of T3 was reversible. A dose of 10 nM L-T3, D-T3, T4, 3,5,3'-triiodothyroacetic, or 3'-isopropyl-3,5-diiodothyronine produced 5- to 15-fold increases in D-III activity after 48 h. In contrast, 10 nM L-thyronine, 3-monoiodothyronine, 3,3'-diiodothyronine, 3,5-diiodothyronine, and rT3 were without effect. A dose of 10 nM T3 or T4 amplified the D-III activity stimulated by 0.1 microM TPA, 20 ng/ml acidic FGF, or 1 mM 8-bromo-cAMP 3- to 8-fold. Otherwise, T3 rapidly inhibited D-II activity. This inhibition was concentration dependent, with a half-maximal effect around 10 nM. In conclusion, thyroid hormones induce D-III activity and potentiate the D-III activity induced by cAMP, TPA, and FGFs in astroglial cells. These reversible effects together with inhibition of D-II activity may contribute to protect the brain against hyperthyroidism.
Esfandiari
A
A
U-96 INSERM, Unité de Recherche sur la Glande Thyroïde et la Régulation Hormonale, Kremlin-Bicêtre, France.
Courtin
F
F
Lennon
A M
AM
Gavaret
J M
JM
Pierre
M
M
D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D007453:Iodide Peroxidase / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D013963:Thyroid Hormones / Q000494:pharmacology*; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology
D013963:Thyroid Hormones; D014284:Triiodothyronine; D007453:Iodide Peroxidase