The role of glucocorticoids in the stress-induced reduction of extrathyroidal 3,5,3'-triiodothyronine generation in rats

Serum concentrations of T₄, T₃, and rT₃ as well as liver and kidney 5'-deiodinase activity, have been examined in rats stressed by restraint. After immobilization, serum concentrations of T₃ decreased significantly (6 hr, -33 ± 1%; 8 h, -42 ± 3%), while serum rT₃ increased (6 h, +55 ± 3%; 8 h, +75 ± 5%). In the same or similarly treated animals, there was a time-dependent reduction in T₄ 5'-deiodinase activity in both liver (4 h, -23 ± 2%; 8 h, -43 ± 3%) and kidney (4 h, -18 ± 1%; 8 h, -42 ± 3%) homogenates. The reduction in hepatic and renal T₃ production was due to reduced enzyme activity and not to reduced substrate availability. In spite of reductions in serum TSH (4 h, -9 ± 1%; 8 h, -51 ± 5%), the serum T₄ concentration did not fall. The serum concentration of corticosterone reached 30 times the basal level after 8 h of restraint. Either adrenalectomy or metyrapone treatment, followed by replacement with nonstress doses of B, completely prevented the alterations of iodothyronine metabolism induced by restraint. These results indicate that the stress-induced elevation of plasma glucorticoids plays a key role in the pathogenesis of the low T₃ syndrome in this model. The reduction in serum T₃ may be accounted for by a reduction in T₃ production by liver and kidney, adding support to the concept that these organs are an important source of plasma T₃ in the rat.