The inner ring (5-) monodeiodination of thyroxine (T4) in cerebral cortex during fetal, neonatal, and adult life

TS Huang, A Beredo, DH Solomon, IJ Chopra - Metabolism, 1986 - Elsevier
TS Huang, A Beredo, DH Solomon, IJ Chopra
Metabolism, 1986Elsevier
Abstract Inner ring (− 5) monodeiodination of T 4 was studied by incubating T 4 (∼ 0.26
μmol/L) with rat cerebral cortical homogenate (∼ 4 mg protein) in the presence of
dithiothreitol (up to 400 mmol/L) and quantifying the amount of the product, rT 3, by a specific
radioimmunoassay. The production of rT 3 was dependent on duration of incubation (up to 2
hours), amount of tissue protein (up to 8 mg), temperature (optimal at 37° C) and pH
(optimal, 7.0) of the incubation mixture and the concentration of DTT (maximally stimulated …
Abstract
Inner ring (−5) monodeiodination of T4 was studied by incubating T4 (∼0.26 μmol/L) with rat cerebral cortical homogenate (∼4 mg protein) in the presence of dithiothreitol (up to 400 mmol/L) and quantifying the amount of the product, rT3, by a specific radioimmunoassay. The production of rT3 was dependent on duration of incubation (up to 2 hours), amount of tissue protein (up to 8 mg), temperature (optimal at 37 °C) and pH (optimal, 7.0) of the incubation mixture and the concentration of DTT (maximally stimulated at 400 mmol/L). The apparent Km and Vmax of the T4-inner ring monodeiodinating activity were 36 nmol/L and 1.75 pmol/mg protein/h, respectively. The activity was inhibited by T3 and 3,5-T2, but not by 3′5′-T2, PTU, methimazole, sodium salicylate, or 8-anilino-I-naphthalene sulfonic acid. Ipodate weakly inhibited T4-to-rT3 monodeiodination. Hyperthyroidism induced by T4 (100 μg/d IP × 3 days), T3 (80 μg/d IP × 3 days) or DIMIT (45 μg/d IP × 3 days) significantly stimulated T4-to-rT3 conversion; DIMIT was the most potent agent. Hypothyroidism inhibited T4-to-rT3 converting activity in cerebral cortex. Fasting for three days had no appreciable effect on T4-to-rT3 conversion in cerebral cortex. Cerebral cortical T4 5-deiodinase activity in the pregnant rat at term was about 50% of that in the adult nonpregnant rat, whereas that in the fetus was about three-fold higher than that in the nonpregnant adult. The values in the mother increased while those in the newborn decreased gradually to become comparable to those in the adult nonpregnant rat by two weeks after delivery. The various data suggest that cerebral cortical T4-to-rT3 converting activity is enzymic in nature and that it is under physiologic regulation.
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