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

Abstract

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)

• Authors: T S Huang, A Beredo, D H Solomon, I J Chopra
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 35 Issue 3 Pg. 272-7 (Mar 1986) ISSN: 0026-0495 [Print] United States
• PMID: 3951360 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Triiodothyronine, Reverse
• Iodine
• Thyroxine
• Dithiothreitol

Topics

• Aging
• Animals
• Cerebral Cortex (embryology, growth & development, metabolism)
• Dithiothreitol (pharmacology)
• Fasting
• Female
• Fetus (metabolism)
• Hydrogen-Ion Concentration
• Hyperthyroidism (metabolism)
• Hypothyroidism (metabolism)
• In Vitro Techniques
• Iodine (metabolism)
• Kinetics
• Male
• Pregnancy
• Rats
• Rats, Inbred Strains
• Thyroxine (metabolism)
• Triiodothyronine, Reverse (biosynthesis)