Enterohepatic circulation of triiodothyronine (T3) in rats:Importance of the microflora for the liberation and reabsorption of T3 from biliary T3 conjugates
In normal rats, T3 glucuronide (T3G) is themajor biliary T3 metabolite, but excretion of T3 sulfate (T3S) isgreatly increased after inhibition of type I deiodinase, e.g. with6-propyl-2-thiouracil (PTU). In this study, the fate of the T3conjugates excreted with bile was studied to assess the significance of a putative enterohepatic circulation of T3 in rats.Conventional (CV) or intestine-decontaminated (ID) rats received iv [125I]T3G or [125I]T3S, the latter usually after pretreatment with PTU (1 mg/100 g BW). Radioactivity in plasma andbile or feces was analyzed by Sephadex LH-20 chromatographyand HPLC. Within 1 h, 88% of injected T3G was excreted inbile of CV or ID rats, independent of PTU. About 75% of theinjected T3S was excreted within 4 h in PTU-treated rats, incontrast to only 20% in controls. Up to 13 h after iv administration of T3G or T3S (+PTU) to intact ID and CV rats, fecalradioactivity consisted of more than 90% T3 in all CV rats, 95%of T3S in T3S-injected ID rats, and 30% T3 and 67% T3G inT3G-injected ID rats. In overnight-fasted CV rats injected withT3G, total plasma radioactivity rapidly declined until a nadir of0.10% dose/ml at about 2.5 h, but radioactivity reappeared witha broad maximum of 0.12% dose/ml between 5.5-10 h. In thelatter phase, plasma radioactivity consisted of predominantly I"and T3 in a ratio of 2:1. Reabsorption was diminished in fed CVrats and prevented in ID rats. Plasma T3 4-10 h after iv T3Ginjection to overnight-fasted CV rats was 12, 2, and 3 timeshigher than that in bile-diverted rats, fed CV rats, and ID rats,respectively, and similar to that 4 h after the injection of T3itself. Total plasma radioactivity as well as plasma T3 6-13 hafter iv administration T3S in PTU-treated rats were significantly increased in CV us. ID rats, e.g. T3 0.016% us. 0.005%dose/ml. These results demonstrate a significant enterohepaticcirculation of T3 in rats in which bacterial hydrolysis of T3conjugates excreted with bile plays an important role. {Endocrinology 125: 2822-2830,1989
