title: Enterohepatic circulation of triiodothyronine (T3) in rats: importance of the microflora for the liberation and reabsorption of T3 from biliary T3 conjugates.
abstract: In normal rats, T3 glucuronide (T3G) is the major biliary T3 metabolite, but excretion of T3 sulfate (T3S) is greatly increased after inhibition of type I deiodinase, e.g. with 6-propyl-2-thiouracil (PTU). In this study, the fate of the T3 conjugates 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 and bile or feces was analyzed by Sephadex LH-20 chromatography and HPLC. Within 1 h, 88% of injected T3G was excreted in bile of CV or ID rats, independent of PTU. About 75% of the injected T3S was excreted within 4 h in PTU-treated rats, in contrast to only 20% in controls. Up to 13 h after iv administration of T3G or T3S (+PTU) to intact ID and CV rats, fecal radioactivity consisted of more than 90% T3 in all CV rats, 95% of T3S in T3S-injected ID rats, and 30% T3 and 67% T3G in T3G-injected ID rats. In overnight-fasted CV rats injected with T3G, total plasma radioactivity rapidly declined until a nadir of 0.10% dose/ml at about 2.5 h, but radioactivity reappeared with a broad maximum of 0.12% dose/ml between 5.5-10 h. In the latter phase, plasma radioactivity consisted of predominantly I- and T3 in a ratio of 2:1. Reabsorption was diminished in fed CV rats and prevented in ID rats. Plasma T3 4-10 h after iv T3G injection to overnight-fasted CV rats was 12, 2, and 3 times higher than that in bile-diverted rats, fed CV rats, and ID rats, respectively, and similar to that 4 h after the injection of T3 itself. Total plasma radioactivity as well as plasma T3 6-13 h after iv administration T3S in PTU-treated rats were significantly increased in CV vs. ID rats, e.g. T3 0.016% vs. 0.005% dose/ml. These results demonstrate a significant enterohepatic circulation of T3 in rats in which bacterial hydrolysis of T3 conjugates excreted with bile plays an important role.
authors.affiliation: Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Rutgers
authors.forename: F A
authors.initials: FA
authors.lastname: Heusdens
authors.forename: F
authors.initials: F
authors.lastname: Bonthuis
authors.forename: W W
authors.initials: WW
authors.lastname: de Herder
authors.forename: M P
authors.initials: MP
authors.lastname: Hazenberg
authors.forename: T J
authors.initials: TJ
authors.lastname: Visser
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D003666:Decontamination; D004755:Enterobacteriaceae / Q000378:metabolism*; D004764:Enterohepatic Circulation / Q000502:physiology*; D005243:Feces / Q000032:analysis; D005965:Glucuronates / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors; D007457:Iodine Radioisotopes; D008297:Male; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000097:blood / Q000378:metabolism* / Q000031:analogs & derivatives
chemical_list: D001798:Blood Proteins; D005965:Glucuronates; D007457:Iodine Radioisotopes; D014284:Triiodothyronine; C054786:triiodothyronine glucuronide; C037673:triiodothyronine sulfate; D011441:Propylthiouracil; D007453:Iodide Peroxidase