Thyroid hormone deiodination pathways in brain and liver of rainbow trout, Oncorhynchus mykiss.
Outer-ring (5') deiodination (ORD) and inner-ring (5) deiodination (IRD) of L-thyroxine (T4) and 3,5,3'-triiodo-L-thyronine (T3) were studied in whole-brain microsomes of rainbow trout and compared with liver deiodination. Brain T4ORD activity (apparent Km = 1.2-2.5 nM; V(max) = 0.10-0.14 pmol/hr/mg microsomal protein) was less than T4IRD activity (apparent Km = 4.9; V(max) = 0.32) and T3IRD activity (apparent Km = 5.2-5.4; V(max) = 1.1-2.0); T3ORD activity was negligible. All three brain deiodinase pathways shared the following properties: pH optima between 7.0 and 7.3, activity enhanced by dithiothreitol (10 mM), weak inhibition by 6-n-propyl-2-thiouracil and iodoacetate, but stronger inhibition by aurothioglucose. Based on competitive inhibition, the substrate preference for brain T4ORD was T4 = tetraiodothyroacetic acid (TETRAC) > 3,3',5'-triiodo-L-thyronine (rT3) > 3,5,3'-triiodothyroacetic acid (TRIAC) >> T3 > 3,5-diiodo-L-thyronine (3,5-T2). A comparable substrate preference profile was obtained for liver T4ORD (Km 1 nM). Both T4IRD and T3IRD in brain had similar substrate preference profiles (rT3 > 3,5-T2 > T4 > T3) which differed from that of T4ORD. Negligible T4IRD and T3IRD activities existed in liver. We conclude that for rainbow trout (i) T4ORD systems in brain and liver are similar, and consistent with a common enzyme that does not match exactly either mammalian type I or II deiodinases, (ii) brain T4IRD and T3IRD enzymes share several common properties, and correspond functionally to the mammalian type III deiodinase, and (iii) under normal physiological conditions the predominant deiodinase pathways in brain (T4IRD and T3IRD) are poised toward T4 and T3 degradation, while that in liver (T4ORD) is poised toward T3 generation.
Frith
S D
SD
Department of Zoology, University of Manitoba, Winnipeg, Canada.
Eales
J G
JG
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D004229:Dithiothreitol / Q000494:pharmacology; D005260:Female; D006863:Hydrogen-Ion Concentration; D007455:Iodine / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013963:Thyroid Hormones / Q000032:analysis / Q000378:metabolism*; D013974:Thyroxine / Q000032:analysis / Q000378:metabolism; D014284:Triiodothyronine / Q000032:analysis / Q000378:metabolism
D013439:Sulfhydryl Reagents; D013963:Thyroid Hormones; D014284:Triiodothyronine; D007455:Iodine; D013974:Thyroxine; D004229:Dithiothreitol