The inner ring (5-) monodeiodination of thyroxine (T 4) in cerebral cortex during fetal, neonatal, and adult life

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 at 400 mmol/L). The apparent Km and Vmax of the T 4-inner ring monodeiodinating activity were 36 nmol/L and 1.75 pmol/mg protein/h, respectively. The activity was inhibited by T 3 and 3,5-T 2, but not by 3′5′-T 2, PTU, methimazole, sodium salicylate, or 8-anilino-I-naphthalene sulfonic acid. Ipodate weakly inhibited T 4-to-rT 3 monodeiodination. Hyperthyroidism induced by T 4 (100 μg/d IP × 3 days), T 3 (80 μg/d IP × 3 days) or DIMIT (45 μg/d IP × 3 days) significantly stimulated T 4-to-rT 3 conversion; DIMIT was the most potent agent. Hypothyroidism inhibited T 4-to-rT 3 converting activity in cerebral cortex. Fasting for three days had no appreciable effect on T 4-to-rT 3 conversion in cerebral cortex. Cerebral cortical T 4 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 T 4-to-rT 3 converting activity is enzymic in nature and that it is under physiologic regulation.