Thyroxine 5-deiodinase in human brain tumors.
To determine whether human brains contain deiodinating pathways, we studied the activity of T4 5-monodeiodinase (5-D) in 20 human brain tumors obtained intraoperatively, including astrocytoma (10), meningioma (4), oligodendroglioma (2), glioblastoma (2), medulloblastoma (1), and malignant lymphoma (1). Mitochondrial-microsomal fractions prepared from these tumor tissues were used as the source of T4 5-D. Each sample was incubated with 32.2 nmol/L T4 and 30 mmol/L dithiothreitol at 37 C for 90 min. T4 5-D activity was measured by the production of rT3 from T4 with a RIA. T4 5-D activity was found in 6 of 10 astrocytomas, 2 oligodendrogliomas, 1 of 2 glioblastomas, and 1 malignant lymphoma. This activity depended on protein concentration, incubation time, incubation temperature, and pH of the incubation mixture. It was also heat labile. T4 5-D was not inhibited by 1 mmol/L propylthiouracil, but was inhibited by iopanoic acid and aurothioglucose in a dose-dependent manner. The apparent Km and maximum velocity for T4 5-D at 30 mmol/L dithiothreitol were 106.6 nmol/L and 22.7 pmol/mg protein.h, respectively. These data suggest that human gliomas (and probably malignant lymphomas) contain T4 5-D activity, which is similar to type III enzyme activity in the rat. T4 5-D may regulate the intracellular concentration of thyroid hormone in gliomas.
Mori
K
K
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Yoshida
K
K
Kayama
T
T
Kaise
N
N
Fukazawa
H
H
Kiso
Y
Y
Kikuchi
K
K
Aizawa
Y
Y
Abe
K
K
D000328:Adult; D000368:Aged; D006051:Aurothioglucose / Q000494:pharmacology; D001932:Brain Neoplasms / Q000201:enzymology*; D002648:Child; D002675:Child, Preschool; D004229:Dithiothreitol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007223:Infant; D007453:Iodide Peroxidase / Q000378:metabolism*; D007480:Iopanoic Acid / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D014285:Triiodothyronine, Reverse / Q000378:metabolism
D006051:Aurothioglucose; D014285:Triiodothyronine, Reverse; D007453:Iodide Peroxidase; D007480:Iopanoic Acid; D004229:Dithiothreitol