Propranolol Decreases Serum Thyroxine as Well as Triiodothyronine in Rats: a Protein-Binding Effect*

Propranolol lowers serum T3 levels in man by reducing 5′-monodeiodination of T4 to T3. Studies of the effect of propranolol on thyroid function in rats are conflicting and have indicated either no change in serum T3 or T4, a decrease in T4 and/or T3, or a rise in T4. In these earlier studies, propranolol was given orally or ip, and in only one was serum propranolol measured to confirm absorption. In an effort to clarify the effect of propranolol on thyroid hormone metabolism in the rat, and to see if the rat could be used as a model for studying the effect of the drug in man, we infused propranolol in Wistar rats by sc implanted osmotic minipumps for 5 days. T4 to T3 conversion in liver and kidney homogenates, as well as serum total T4, total T3, and per cent dialyzable T4 (%DT4) and T3 (%DT3), were examined in intact an d thyroidectomized, T4-replaced propranolol-treated and control rats. The results showed that, at a mean serum propranolol concentration of 162 ng/ml, serum total T3 fell (P < 0.01) as did total T4 (P < 0.001), whereas there was no significant decrease in T4 to T3 conversion in liver or kidney homogenates. There was also no change in 3′5′-diiodothyronine to 3′-monoiodothyronine conversion in liver homogenates. At similar propranolol concentrations, the %DT3 and %DT4 rose (P < 0.005). TSH and free T3 did not change, whereas free T4 fell slightly (P < 0.05) in one experiment and was normal in a second. In thyroidectomized T4-replaced animals, total T4 fell (P < 0.05), total T3 fell (P < 0.01), the %DT4 rose (P < 0.025), the %DT3 rose but not significantly, and free T3 fell slightly. Although propranolol (10-4 M) added in vitro partially inhibited T4 to T3 conversion in liver and kidney homogenates, this concentration was considerably greater than the highest mean serum level achieved of 162 ng/ml (0.6 μM). The results indicate that, in Wistar rats, propranolol infusions decrease both serum T3 and T4 by altering thyroid hormone binding and not by inhibiting peripheral T4-5′-monodeiodination as occurs in man.