This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zavacki, A. M. Articles by Bianco, A. C. Search for Related Content PubMed PubMed Citation Articles by Zavacki, A. M. Articles by Bianco, A. C.

Type 1 Iodothyronine Deiodinase Is a Sensitive Marker of Peripheral Thyroid Status in the Mouse

Thyroid Section (A.M.Z., M.A.C., E.S., J.W.H., P.R.L., A.C.B.), Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Boston, Massachusetts 02115; Laboratory of Comparative Endocrinology (G.A.), Katholieke Universiteit Leuven, 3000 Leuven, Belgium; and Gene Regulation Section (H.Y., S.C.), Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Ann Marie Zavacki, Ph.D., Brigham and Women’s Hospital, 77 Avenue Louis Pasteur, HIM 641, Boston, Massachusetts 02115. E-mail: azavacki{at}rics.bwh.harvard.edu.

Mice with one thyroid hormone receptor (TR) -1 allele encoding a dominant negative mutant receptor (TR1^PV/+) have persistently elevated serum T₃ levels (1.9-fold above normal). They also have markedly increased hepatic type 1 iodothyronine deiodinase (D1) mRNA and enzyme activity (4- to 5-fold), whereas other hepatic T₃-responsive genes, such as Spot14 and mitochondrial -glycerol phosphate dehydrogenase (-GPD), are only 0.7-fold and 1.7-fold that of wild-type littermates (TR1^+/+). To determine the cause of the disproportionate elevation of D1, TR1^+/+ and TR1^PV/+ mice were rendered hypothyroid and then treated with T₃. Hypothyroidism decreased hepatic D1, Spot14, and -GPD mRNA to similar levels in TR1^+/+ and TR1^PV/+ mice, whereas T₃ administration caused an approximately 175-fold elevation of D1 mRNA but only a 3- to 6-fold increases in Spot14 and -GPD mRNAs. Interestingly, the hypothyroidism-induced increase in cerebrocortical type 2 iodothyronine deiodinase activity was 3 times greater in the TR1^PV/+ mice, and these mice had no T₃-dependent induction of type 3 iodothyronine deiodinase. Thus, the marked responsiveness of hepatic D1 to T₃ relative to other genes, such as Spot14 and -GPD, explains the relatively large effect of the modest increase in serum T₃ in the TR1^PV/+ mice, and TR plays a key role in T₃-dependent positive and negative regulation of the deiodinases in the cerebral cortex.

This article has been cited by other articles:

				D. T. Szabo, V. M. Richardson, D. G. Ross, J. J. Diliberto, P. R. S. Kodavanti, and L. S. Birnbaum Effects of Perinatal PBDE Exposure on Hepatic Phase I, Phase II, Phase III, and Deiodinase 1 Gene Expression Involved in Thyroid Hormone Metabolism in Male Rat Pups Toxicol. Sci., January 1, 2009; 107(1): 27 - 39. [Abstract] [Full Text] [PDF]

				P. Pelletier, K. Gauthier, O. Sideleva, J. Samarut, and J. E. Silva Mice Lacking the Thyroid Hormone Receptor-{alpha} Gene Spend More Energy in Thermogenesis, Burn More Fat, and Are Less Sensitive to High-Fat Diet-Induced Obesity Endocrinology, December 1, 2008; 149(12): 6471 - 6486. [Abstract] [Full Text] [PDF]

				Y. Debaveye, B. Ellger, L. Mebis, T. J. Visser, V. M. Darras, and G. Van den Berghe Effects of Substitution and High-Dose Thyroid Hormone Therapy on Deiodination, Sulfoconjugation, and Tissue Thyroid Hormone Levels in Prolonged Critically Ill Rabbits Endocrinology, August 1, 2008; 149(8): 4218 - 4228. [Abstract] [Full Text] [PDF]

				W. T. Festuccia, S. Oztezcan, M. Laplante, M. Berthiaume, C. Michel, S. Dohgu, R. G. Denis, M. N. Brito, N. A. Brito, D. S. Miller, et al. Peroxisome Proliferator-Activated Receptor-{gamma}-Mediated Positive Energy Balance in the Rat Is Associated with Reduced Sympathetic Drive to Adipose Tissues and Thyroid Status Endocrinology, May 1, 2008; 149(5): 2121 - 2130. [Abstract] [Full Text] [PDF]

				L. P. Klieverik, H. P. Sauerwein, M. T. Ackermans, A. Boelen, A. Kalsbeek, and E. Fliers Effects of thyrotoxicosis and selective hepatic autonomic denervation on hepatic glucose metabolism in rats Am J Physiol Endocrinol Metab, March 1, 2008; 294(3): E513 - E520. [Abstract] [Full Text] [PDF]

				C. Fekete, B. C. G. Freitas, A. Zeold, G. Wittmann, A. Kadar, Z. Liposits, M. A. Christoffolete, P. Singru, R. M. Lechan, A. C. Bianco, et al. Expression Patterns of WSB-1 and USP-33 Underlie Cell-Specific Posttranslational Control of Type 2 Deiodinase in the Rat Brain Endocrinology, October 1, 2007; 148(10): 4865 - 4874. [Abstract] [Full Text] [PDF]

				M. D. Erion, E. E. Cable, B. R. Ito, H. Jiang, J. M. Fujitaki, P. D. Finn, B.-H. Zhang, J. Hou, S. H. Boyer, P. D. van Poelje, et al. From the Cover: Targeting thyroid hormone receptor-beta agonists to the liver reduces cholesterol and triglycerides and improves the therapeutic index PNAS, September 25, 2007; 104(39): 15490 - 15495. [Abstract] [Full Text] [PDF]

				C. S. Kim, H. Ying, M. C. Willingham, and S.-y. Cheng The pituitary tumor-transforming gene promotes angiogenesis in a mouse model of follicular thyroid cancer Carcinogenesis, May 1, 2007; 28(5): 932 - 939. [Abstract] [Full Text] [PDF]

				H. Ying, O. Araki, F. Furuya, Y. Kato, and S.-Y. Cheng Impaired Adipogenesis Caused by a Mutated Thyroid Hormone {alpha}1 Receptor Mol. Cell. Biol., March 15, 2007; 27(6): 2359 - 2371. [Abstract] [Full Text] [PDF]

				M. A. Christoffolete, R. Arrojo e Drigo, F. Gazoni, S. M. Tente, V. Goncalves, B. S. Amorim, P. R. Larsen, A. C. Bianco, and A. M. Zavacki Mice with Impaired Extrathyroidal Thyroxine to 3,5,3'-Triiodothyronine Conversion Maintain Normal Serum 3,5,3'-Triiodothyronine Concentrations Endocrinology, March 1, 2007; 148(3): 954 - 960. [Abstract] [Full Text] [PDF]

				F. Flamant, J. D. Baxter, D. Forrest, S. Refetoff, H. Samuels, T. S. Scanlan, B. Vennstrom, and J. Samarut International Union of Pharmacology. LIX. The Pharmacology and Classification of the Nuclear Receptor Superfamily: Thyroid Hormone Receptors Pharmacol. Rev., December 1, 2006; 58(4): 705 - 711. [Full Text] [PDF]

				D C Thijssen-Timmer, M P.-T. Schiphorst, J Kwakkel, R Emter, A Kralli, W M Wiersinga, and O Bakker PGC-1{alpha} regulates the isoform mRNA ratio of the alternatively spliced thyroid hormone receptor {alpha} transcript. J. Mol. Endocrinol., October 1, 2006; 37(2): 251 - 257. [Abstract] [Full Text] [PDF]

				L. Schomburg, C. Riese, M. Michaelis, E. Griebert, M. O. Klein, R. Sapin, U. Schweizer, and J. Kohrle Synthesis and Metabolism of Thyroid Hormones Is Preferentially Maintained in Selenium-Deficient Transgenic Mice Endocrinology, March 1, 2006; 147(3): 1306 - 1313. [Abstract] [Full Text] [PDF]

				M. J. Schneider, S. N. Fiering, B. Thai, S.-y. Wu, E. St. Germain, A. F. Parlow, D. L. St. Germain, and V. A. Galton Targeted Disruption of the Type 1 Selenodeiodinase Gene (Dio1) Results in Marked Changes in Thyroid Hormone Economy in Mice Endocrinology, January 1, 2006; 147(1): 580 - 589. [Abstract] [Full Text] [PDF]

				R. P. Peeters, S. van der Geyten, P. J. Wouters, V. M. Darras, H. van Toor, E. Kaptein, T. J. Visser, and G. Van den Berghe Tissue Thyroid Hormone Levels in Critical Illness J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6498 - 6507. [Abstract] [Full Text] [PDF]