Endocrinology, Vol 128, 1717-1722, Copyright © 1991 by Endocrine Society

ARTICLES

The ontogeny of iodothyronine deiodinase systems in liver and intestine of the rat

VA Galton, PT McCarthy and DL St Germain
Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03756.

The ontogeny of the iodothyronine deiodinase systems has been studied by several investigators in recent years, but our understanding of the subject is far from complete. The present study was conducted to obtain kinetic information concerning 5' deiodinase (5'D) and 5 deiodinase (5D) activities in fetal rat liver and intestine, and to examine reduced glutathione (GSH)-activated 5'D activity in the two tissues. When dithiothreitol (DTT) was used as cofactor in concentrations up to 100 mM, 5'D activity was not clearly detected in liver or intestine until day 16 of gestation. Activity increased markedly in both tissues between fetal day 18-21, due primarily to an increase in maximum velocity (Vmax) of the enzyme. However, whereas 5'D activity was much higher in adult liver than in fetal liver [due to both an increase in Vmax and a decrease in the Michaelis-Menten constant (Km)], activity was barely detectable in adult intestine. When GSH was used as cofactor, the temporal development of activity in both tissues was comparable to that observed with DTT, but kinetic values were very different; with DTT mean values for Vmax in liver ranged from 3.7-1264 pmol I-/h.mg protein, and values for Km ranged from 0.1-0.5 microM; with GSH, values for Vmax ranged from 0.4-16.7 pmol I-/h.mg protein, and values for Km were less than 1 nM. A comparable difference was observed also in intestine. When either DTT or GSH was used as cofactor, 5'D activity was inhibited in the presence of 6n-propyl-2- thiouracil or iopanoic acid. Using T3 as substrate it was found that 5D activity was much higher in intestine than in liver, and the amount of 5D activity in intestine paralleled that in brain in that it was much higher in fetal than in adult tissue. Moreover, values for Vmax and Km in fetal intestine were comparable to those in fetal brain. These findings suggest that thyroid hormone is important in the developing rat intestine and raise the possibility that GSH could be the activator of 5'D systems in vivo.

This article has been cited by other articles:

				A. Coppola, R. Meli, and S. Diano Inverse Shift in Circulating Corticosterone and Leptin Levels Elevates Hypothalamic Deiodinase Type 2 in Fasted Rats Endocrinology, June 1, 2005; 146(6): 2827 - 2833. [Abstract] [Full Text] [PDF]

				F. W. J. S. Wassen, W. Klootwijk, E. Kaptein, D. J. Duncker, T. J. Visser, and G. G. J. M. Kuiper Characteristics and Thyroid State-Dependent Regulation of Iodothyronine Deiodinases in Pigs Endocrinology, September 1, 2004; 145(9): 4251 - 4263. [Abstract] [Full Text] [PDF]

				M. H. A. Kester, E. Kaptein, T. J. Roest, C. H. van Dijk, D. Tibboel, W. Meinl, H. Glatt, M. W. H. Coughtrie, and T. J. Visser Characterization of rat iodothyronine sulfotransferases Am J Physiol Endocrinol Metab, September 1, 2003; 285(3): E592 - E598. [Abstract] [Full Text] [PDF]

				G. G. J. M. Kuiper, W. Klootwijk, and T. J. Visser Substitution of Cysteine for Selenocysteine in the Catalytic Center of Type III Iodothyronine Deiodinase Reduces Catalytic Efficiency and Alters Substrate Preference Endocrinology, June 1, 2003; 144(6): 2505 - 2513. [Abstract] [Full Text] [PDF]

				C. A. Shepherdley, C. B. Daniels, S. Orgeig, S. J. Richardson, B. K. Evans, and V. M. Darras Glucocorticoids, thyroid hormones, and iodothyronine deiodinases in embryonic saltwater crocodiles Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2002; 283(5): R1155 - R1163. [Abstract] [Full Text] [PDF]

				A. C. Bianco, D. Salvatore, B. Gereben, M. J. Berry, and P. R. Larsen Biochemistry, Cellular and Molecular Biology, and Physiological Roles of the Iodothyronine Selenodeiodinases Endocr. Rev., February 1, 2002; 23(1): 38 - 89. [Abstract] [Full Text] [PDF]

				J. M. Bates, D. L. St. Germain, and V. A. Galton Expression Profiles of the Three Iodothyronine Deiodinases, D1, D2, and D3, in the Developing Rat Endocrinology, February 1, 1999; 140(2): 844 - 851. [Abstract] [Full Text]

				K. Richard, R. Hume, E. Kaptein, J. P. Sanders, H. van Toor, W. W. de Herder, J. C. den Hollander, E. P. Krenning, and T. J. Visser Ontogeny of Iodothyronine Deiodinases in Human Liver J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2868 - 2874. [Abstract] [Full Text]

				A. Hernandez, D. L. St. Germain, and M. J. Obregon Transcriptional Activation of Type III Inner Ring Deiodinase by Growth Factors in Cultured Rat Brown Adipocytes Endocrinology, February 1, 1998; 139(2): 634 - 639. [Abstract] [Full Text] [PDF]