SERUM IODOTHYRONINE CONCENTRATIONS IN INTESTINALLY DECONTAMINATED RATS TREATED WITH A 5'-DEIODINASE TYPE-I INHIBITOR 6-ANILINO-2-THIOURACIL

Enteric bacteria have been postulated to have a role in thyroid econom y by promoting the hydrolysis of thyroid hormone conjugates of biliary origin, thus permitting the absorption and recycling of thyroxine (T- 4) and triiodothyronine (T-3). An enterohepatic circulation of T-3 mig ht be more pronounced under conditions in which type I iodothyronine d eiodinase activity (5'D-I) is inhibited, because this augments the acc umulation of T-3 sulfate conjugates in bile. This potential of increas ed gut reabsorption of T-3 might explain, at least in part, the failur e of serum T-3 values to decrease appreciably when marked reductions i n peripheral 5'D-I activity are induced by selenium deficiency or 6-an ilino-2-thiouracil (ATU) administration. Thus, studies were performed to determine the effect of intestinal decontamination, in the absence and in the presence of 5'D-I inhibition, on plasma T-4 and T-3 concent rations. Groups of adult male rats received either enteric antibiotics or no antibiotics for 12 days and then, in half of the rats in each g roup, treatment for 10 days with ATU, a 5'D-I inhibitor that does not affect thyroid hormone synthesis. The activity of intestinal arylsulfa tase and arylsulfotransferase, enzymes that catalyze hydrolysis of thy roid hormone conjugates, was reduced markedly by approximately 87% in rats that received antibiotics, regardless of whether or not they also received ATU, The ATU treatment markedly inhibited liver 5'D-I activi ty in antibiotic-treated as well as in non-antibiotic-treated rats (co ntrol = 399 +/- 32 U/mg protein (mean +/- SEM); ATU = 152 +/- 17; anti biotics = 351 +/- 29; antibiotics + ATU = 130 +/- 10; p < 0.01) and si gnificantly increased plasma T-4 and T-3 sulfate (T4S, T3S) concentrat ions (control: T4S = 2.8 +/- 0.4 and T3S = 6.7 +/- 1.3 ng/dl: ATU: T4S = 6.2 +/- 1.4 and T3S = 10.6 +/- 2.1 ng/dl; antibiotics: T4S = 1.8 +/ - 0.2 and T3S = 3.6 +/- 1.0 ng/dl; antibiotics + ATU: T4S = 6.8 +/- 0. 7 and T3S = 9.7 +/- 1.8 ng/dl: p < 0.05). The ATU treatment was associ ated with a significant increase in plasma T-4 and rT(3) concentration s but did not affect plasma T-3 concentrations, and intestinal deconta mination did not alter these ATU-associated effects on circulating thy roid hormones. These results suggest that anaerobic enteric bacteria i n the rat do not have an important role in recycling of thyroid hormon es, either under normal conditions or in circumstances where 5'D-I act ivity is markedly reduced, and that increased gut absorption of T-3 fr om T3S cannot explain the near-normal serum T-3 values found when peri pheral 5'D-I activity is markedly decreased.