Thyroid hormone deiodinase systems in salmonids,and their involvement in the regulation of thyroidal status

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 (V_max) 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.