title: Thyroid hormone deiodinase systems in salmonids, and their involvement in the regulation of thyroidal status.
abstract: The trout thyroid secretes L-thyroxine (T4) which undergoes enzymatic deiodination in liver and other tissues. Based on mammalian studies, T4 outer-ring deiodination (ORD) or T4 inner-ring deiodination (IRD) could generate respectively 3,5,3'-triiodo-L-thyronine (T3) or 3,3',5'-T3(rT3), while subsequent T3ORD or T3IRD could generate respectively 3,5-diiodo-L-thyronine (T2) or 3,3'-T2, and rT3ORD or rT3IRD could generate respectively 3,3'-T2 or 3',5'-T2. In practice, T4 in trout undergoes hepatic ORD to produce T3 but negligible IRD to produce rT3, and T3 in turn undergoes negligible ORD but modest IRD to produce 3,3'-T2. T4ORD, which is particularly important in converting T4 to the biologically more potent T3, also occurs in gill, muscle and kidney. At least two isozymes are involved: i) a high-affinity, propylthiouracil (PTU)-sensitive T4ORD which displays ping-pong kinetics, requires thiol as a cofactor, and is present in liver, gill and muscle, and ii) a low-affinity, PTU-insensitive T4ORD with sequential kinetics with a thiol cofactor, and is present in liver and kidney. Receptor-bound T3 is derived primarily from the plasma for kidney, mainly from intracellular sources for gill and about equally from both plasma and intracellular sources for liver. Thus, the high-affinity T4ORD may produce T3 for local intracellular use while the low-affinity 5'-monodeiodinase may produce T3 for systemic use. T4ORD activity responds to nutritional factors and the physiologic state of the fish. Furthermore, T3 administered orally for either 6 weeks or 24h reduces the functional level (Vmax) of hepatic T4ORD, and T3 added to isolated hepatocytes also reduces activity, indicating direct T3 autoregulation of T4ORD to maintain hepatocyte T3 homeostasis. However, T3 administration also induces T4IRD to produce biologically inactive rT3 and induces T3IRD to produce 3,3'-T2. Thus, the trout liver has several iodothyronine deiodinase systems which in a coordinated manner regulate tissue T3 homeostasis in the face of a T3 challenge. It does this by decreasing formation of T3 itself, by diverting T4 substrate to biologically inactive rT3 and by increasing the degradation of T3. These deiodinases differ in many respects from any mammalian counterparts.
authors.affiliation: Department of Zoology, University of Manitoba, Winnipeg, Manitoba, R3T 2N2, Canada.
authors.forename: J G
authors.initials: JG
authors.lastname: Eales
authors.forename: D L
authors.initials: DL
authors.lastname: Maclatchy
authors.forename: R M
authors.initials: RM
authors.lastname: Sweeting