In vitro studies of the effect of propylthiouracil and ronnel on thyroxine-5'-monodeiodinase activity in steers.

This study compares in vitro effects of propylthiouracil (PTU) and ronnel on the conversion of thyroxine (T4) to triiodothyronine (T3) in liver and kidney from Angus steers. Tissues were homogenized and incubated with T4 (1.3 microM) in the presence of 0 to 59 microM PTU or 0 to 49.7 microM ronnel. The T3 generated during a 30-min incubation was measured by radioimmunoassay. It was found that 1.47, 5.9 and 59 microM PTU decreased T4 to T3 conversion in liver and kidney by 62 and 88, 71 and 100, and 81 and 100%, respectively. The inhibition caused by 1.47 and 5.9 microM PTU was overcome by addition of 2 mM dithiothreitol (DTT). Ronnel in concentrations of 1.24, 6.22, 49.7 microM decreased T4 to T3 conversion in liver and kidney 46 and 45, 51 and 72, and 78 and 95%, respectively. However, with ronnel, the addition of DTT caused further inhibition. A Lineweaver-Burk plot of the data obtained using .32 to 6.43 microM T4 with 1.47 and 5.9 microM PTU or 6.22 and 12.44 microM ronnel indicated that PTU is an uncompetitive inhibitor (Ki = 1.67 microM) and ronnel is a noncompetitive (Ki = 15.5 microM) inhibitor of T4-5'-monodeiodination. The data suggest that decreased conversion of T4 to T3 by PTU or ronnel may be responsible for the increased plasma concentrations of T4 and slightly decreased plasma concentrations of T3 reported in steers treated with levels of both PTU and ronnel that are associated with growth stimulation.