Effects of Thiouracil on Rat Liverα-Glycerophosphate Dehydrogenase and Serum PBI Responses tol-Thyroxine

Abstract

The effects of dietary thiouracil (TU) were studied on rat liver mito-chondrial [alpha] -glycerophosphate dehydrogenase (GPD) and serum protein bound iodine (PBI) responses to L-thyroxine (T4) given by sc injection or by gavage. Although serum turnover rates of a single dose of 131I-T4 were not affected by TU, the half-life of serum PB131I averaged 22 hr for injected and 30 hr for gavaged animals. Maximum serum PB131I levels were reached in 8-10 hr in all groups following a single dose of 131I-T4 but the PBI levels were approximately 3 times higher in injected than in gavaged animals. This observation correlates with the previous finding that injected T4 is approximately 3 times more active than oral T4 in the rat. In all experiments, graded doses of T4 given to rats receiving 0.2 g TU/100 g diet resulted in high PBI levels (up to 100 [mu]g/100 ml serum) but suboptimal GPD responses. When the amount of TU in the diet was increased from 0 to 0.8 g/100 g diet, animals receiving 9 [mu]g T4/IOO g body weight/day showed a progressive increase in serum PBI concentrations and a progressive decrease in the liver GPD response. Thus, circulating T4 (PBI) showed a progressive loss in physiological activity as the amount of TU in the diet was increased.