Endocrinology, Vol 123, 2303-2311, Copyright © 1988 by Endocrine Society

ARTICLES

Characterization of triiodothyronine transport and accumulation in rat erythrocytes

J Osty, L Jego, J Francon and JP Blondeau
Unite de Recherche sur la Glande Thyroide et la Regulation Hormonale (U.96) de I'Institut National de la Sante et de la Recherche Medicale, Le Kremlin-Bicetre, France.

The transport of L-T3 was studied in washed rat erythrocytes. L-T3 uptake was temperature sensitive: the initial velocity of uptake at low substrate concentration was 40 times higher at 37 C than at 0C whereas, at equilibrium, the ratio of cell-associated to extracellular L-T3 was about 7 times lower at 37 C than at 0 C. When [125I]L-T3-loaded erythrocytes were diluted into a serum albumin-containing medium, the efflux of L-T3 proceeded at a rate similar to that of influx. A large excess of unlabeled L-T3 in the medium blocked influx and efflux of labeled L-T3, indicating a saturable carrier-mediated transport process across the plasma membrane. the transport obeyed simple Michaelis- Menten kinetics with an apparent Km of 53 nM and a Vmax of 4.3 pmol/min.10(8) cells at 0 C. The Km increased only slightly with temperature whereas the Vmax was 100 times higher at 37 than at 0 C. The Arrhenius activation energy of uptake was 21 Cal/mol. The nonsaturable adsorption of L-T3 to the cells did not exceed 1% of the equilibrium levels at 0 C and 10% at 37 C. Uptake of L-T3 was very specific: unlabeled L-T4, D-T3, triiodothyroacetic acid, rT3, and DL- thyronine inhibited uptake with inhibition constant (Ki) values which were 35, 60, 65, 110, and 250 times, respectively, greater than the Km of L-T3. [125I]L-T4 uptake was negligible. L-T3 uptake and L-T4 inhibition of L-T3 uptake were pH dependent. It is suggested that only the unionized 4'-OH forms of the hormones were recognized by the transport system. At equilibrium, L-T3 was accumulated within the cell (apparent intracellular concentration approximately 50 times higher than that in the medium at 37 C). However, uptake was not dependent on the transmembrane Na+ gradient, suggesting facilitated rather than active transport. Analysis of L-T3 binding to erythrocyte cytosolic proteins suggested that they were implicated in the intracellular trapping of L-T3. At a concentration of 5 x 10(9) erythrocytes/ml (approximately the blood concentration), the amount of L-T3 accumulated in the cells was 13.5 times higher than the extracellular amount. We conclude that L-T3 is solely transported by a saturable, stereospecific, and Na+-independent carrier system. The intracellular accumulation and the rapid transmembrane movements of L-T3 suggest that erythrocytes might play a role in the interorgan transport of L-T3.

This article has been cited by other articles:

				T. Murata and K. Yamauchi Low-Temperature Arrest of the Triiodothyronine-Dependent Transcription in Rana catesbeiana Red Blood Cells Endocrinology, January 1, 2005; 146(1): 256 - 264. [Abstract] [Full Text] [PDF]

				N Shimada and K Yamauchi Characteristics of 3,5,3'-triiodothyronine (T3)-uptake system of tadpole red blood cells: effect of endocrine-disrupting chemicals on cellular T3 response J. Endocrinol., December 1, 2004; 183(3): 627 - 637. [Abstract] [Full Text] [PDF]

				A. Ito, K. Yamaguchi, T. Onogawa, M. Unno, T. Suzuki, T. Nishio, T. Suzuki, H. Sasano, T. Abe, and M. Tamai Distribution of Organic Anion-Transporting Polypeptide 2 (oatp2) and oatp3 in the Rat Retina Invest. Ophthalmol. Vis. Sci., March 1, 2002; 43(3): 858 - 863. [Abstract] [Full Text] [PDF]

				G. Hennemann, R. Docter, E. C. H. Friesema, M. de Jong, E. P. Krenning, and T. J. Visser Plasma Membrane Transport of Thyroid Hormones and Its Role in Thyroid Hormone Metabolism and Bioavailability Endocr. Rev., August 1, 2001; 22(4): 451 - 476. [Abstract] [Full Text] [PDF]

				K. Fujiwara, H. Adachi, T. Nishio, M. Unno, T. Tokui, M. Okabe, T. Onogawa, T. Suzuki, N. Asano, M. Tanemoto, et al. Identification of Thyroid Hormone Transporters in Humans: Different Molecules Are Involved in a Tissue-Specific Manner Endocrinology, May 1, 2001; 142(5): 2005 - 2012. [Abstract] [Full Text]

				R. R. Cavalieri, L. A. Simeoni, S. W. Park, J. D. Baxter, B. F. Scharschmidt, R. C. J. Ribeiro, and N. Lomri Thyroid Hormone Export in Rat FRTL-5 Thyroid Cells and Mouse NIH-3T3 Cells Is Carrier-Mediated, Verapamil-Sensitive, and Stereospecific Endocrinology, November 1, 1999; 140(11): 4948 - 4954. [Abstract] [Full Text]

				T. Abe, M. Kakyo, H. Sakagami, T. Tokui, T. Nishio, M. Tanemoto, H. Nomura, S. C. Hebert, S. Matsuno, H. Kondo, et al. Molecular Characterization and Tissue Distribution of a New Organic Anion Transporter Subtype (oatp3) That Transports Thyroid Hormones and Taurocholate and Comparison with oatp2 J. Biol. Chem., August 28, 1998; 273(35): 22395 - 22401. [Abstract] [Full Text] [PDF]