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Enterohepatic Circulation of Triiodothyronine (T₃) in Rats: Importance of the Microflora for the Liberation and Reabsorption of T₃ from Biliary T₃ Conjugates^*

Departments of Internal Medicine III Rotterdam, The Netherlands
Internal Medicine I Rotterdam, The Netherlands
Medical Microbiology, Erasmus University Medical School Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Theo J. Visser, Ph.D., Department of Internal Medicine III, Erasmus University Medical School, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands

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 us. ID rats, e.g. T₃ 0.016% us. 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.

Footnotes

^* Presented in part at the 16th Annual Meeting of the European Thyroid Association, Lausanne, Switzerland, July 5–10, 1987, and was reported previously [Ann Endocrinol 48:134, 1987 (Abstract)]. This work was supported in part by the Foundation for Medical Research MEDIGON(Grant 900–540–191).

Received May 17, 1989.

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