The inner ring (5-) monodeiodination of thyroxine (T4) in cerebral cortex during fetal, neonatal, and adult life.
Inner ring (-5) monodeiodination of T4 was studied by incubating T4 (approximately 0.26 mumol/L) with rat cerebral cortical homogenate (approximately 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 degrees 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 micrograms/d IP X 3 days), T3 (80 micrograms/d IP X 3 days) or DIMIT (45 micrograms/d IP X 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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000375:Aging; D000818:Animals; D002540:Cerebral Cortex / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D005215:Fasting; D005260:Female; D005333:Fetus / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006980:Hyperthyroidism / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism; D066298:In Vitro Techniques; D007455:Iodine / Q000378:metabolism; D007700:Kinetics; D008297:Male; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013974:Thyroxine / Q000378:metabolism*; D014285:Triiodothyronine, Reverse / Q000096:biosynthesis*
D014285:Triiodothyronine, Reverse; D007455:Iodine; D013974:Thyroxine; D004229:Dithiothreitol