Endocrinology, Vol 131, 2559-2564, Copyright © 1992 by Endocrine Society

ARTICLES

Ontogeny of hepatic nuclear triiodothyronine receptor isoforms in the rat

C Rodd, HL Schwartz, KA Strait and JH Oppenheimer
Department of Medicine, University of Minnesota, Minneapolis 55455.

We have determined the contribution of the thyroid hormone receptor (TR) isoforms TR alpha 1 and TR beta 1 to the postnatal rise in rat hepatic nuclear T3-binding capacity. In agreement with previous studies, total hepatic nuclear binding capacity rose by about 8-fold from the 19th day of gestation to young adulthood at 2 months of age (0.10 +/- 0.03 to 0.86 +/- 0.17 pmol/mg DNA). The levels of specific TR species were measured by immunoprecipitation of T3-binding activity from hepatic extracts using a panel of antisera directed against specific regions of the TR isoforms. The difference between receptor immunoprecipitated with antibody against TR beta 1 and that precipitated with an antibody against an identical region in both TR beta 1 and TR alpha 1 was tentatively assumed to represent TR alpha 1. TR alpha 1 accounted for virtually all T3-binding activity in fetal liver on gestational day 19 (G19), increased by 2-fold shortly after birth, and remained constant thereafter. TR alpha 1 mRNA, on the other hand, was highest in concentration on G16 and fell by 50-75% in the adult. TR beta 1 was undetectable by immunoprecipitation of hepatic extracts from fetuses on G19. However, Northern analysis showed the presence of TR beta 1 mRNA in the fetal liver, which rose in concentration by 3- to 4-fold in late gestation and then remained constant. The contribution of TR beta 1 to total binding capacity rose to 33% and 40% on postnatal days 15 and 30, respectively, and to 80% in the adult liver. Immunohistochemical analyses of hepatic sections confirmed the presence of very low levels of TR beta 1 in fetal liver as early as G16 and G19, and a sharp rise in TR beta 1 protein concentration in the postnatal period. This indicated that the increase in TR beta 1-binding capacity results from increased TR beta 1 mass. The increase in TR beta 1-binding capacity, thus, is due to increased translational efficiency of the beta 1 mRNA or stabilization of the TR beta 1 protein. The prominence of TR alpha 1 in both rat fetal liver and fetal brain, as previously demonstrated in our laboratory, raises the possibility that this receptor isoform may carry out specialized functions in the fetus and that TR beta 1 subserves still other functions at later stages of development.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				E. Silvestri, A. Lombardi, P. de Lange, L. Schiavo, A. Lanni, F. Goglia, T. J. Visser, and M. Moreno Age-related changes in renal and hepatic cellular mechanisms associated with variations in rat serum thyroid hormone levels Am J Physiol Endocrinol Metab, June 1, 2008; 294(6): E1160 - E1168. [Abstract] [Full Text] [PDF]

				M. Alonso, C. Goodwin, X. Liao, D. Page, S. Refetoff, and R. E. Weiss Effects of Maternal Levels of Thyroid Hormone (TH) on the Hypothalamus-Pituitary-Thyroid Set Point: Studies in TH Receptor {beta} Knockout Mice Endocrinology, November 1, 2007; 148(11): 5305 - 5312. [Abstract] [Full Text] [PDF]

				R. Keijzer, P.-J. E Blommaart, W. T Labruyere, J. L M Vermeulen, B. Z. Doulabi, O. Bakker, D. Tibboel, and W. H Lamers Expression of thyroid hormone receptors A and B in developing rat tissues; evidence for extensive posttranscriptional regulation J. Mol. Endocrinol., May 1, 2007; 38(5): 523 - 535. [Abstract] [Full Text] [PDF]

				C. G. Vallejo, A. M. Seguido, P. S. Testillano, and M.-C. Risueno Thyroid hormone regulates tubulin expression in mammalian liver. Effects of deleting thyroid hormone receptor-{alpha} or -{beta} Am J Physiol Endocrinol Metab, July 1, 2005; 289(1): E87 - E94. [Abstract] [Full Text] [PDF]

				L. Jackson-Hayes, S. Song, E. N. Lavrentyev, M. S. Jansen, F. B. Hillgartner, L. Tian, P. A. Wood, G. A. Cook, and E. A. Park A Thyroid Hormone Response Unit Formed between the Promoter and First Intron of the Carnitine Palmitoyltransferase-Ialpha Gene Mediates the Liver-specific Induction by Thyroid Hormone J. Biol. Chem., February 28, 2003; 278(10): 7964 - 7972. [Abstract] [Full Text] [PDF]

				B. Zandieh Doulabi, M. Platvoet-ter Schiphorst, H. C. van Beeren, W. T. Labruyere, W. H. Lamers, E. Fliers, O. Bakker, and W. M. Wiersinga TR{beta}1 Protein Is Preferentially Expressed in the Pericentral Zone of Rat Liver and Exhibits Marked Diurnal Variation Endocrinology, March 1, 2002; 143(3): 979 - 984. [Abstract] [Full Text] [PDF]

				P. WHITE, K. A. BURTON, A. L. FOWDEN, and M. J. DAUNCEY Developmental expression analysis of thyroid hormone receptor isoforms reveals new insights into their essential functions in cardiac and skeletal muscles FASEB J, June 1, 2001; 15(8): 1367 - 1376. [Abstract] [Full Text] [PDF]

				S. Torres, B. P. Diaz, J. J. Cabrera, J. C. Diaz-Chico, B. N. Diaz-Chico, and A. Lopez-Guerra Thyroid hormone regulation of rat hepatocyte proliferation and polyploidization Am J Physiol Gastrointest Liver Physiol, January 1, 1999; 276(1): G155 - G163. [Abstract] [Full Text] [PDF]

				X.-G. Zhu, P. McPhie, K.-H. Lin, and S.-Y. Cheng The Differential Hormone-dependent Transcriptional Activation of Thyroid Hormone Receptor Isoforms Is Mediated by Interplay of Their Domains J. Biol. Chem., April 4, 1997; 272(14): 9048 - 9054. [Abstract] [Full Text] [PDF]

				R. J. Denver, S. Pavgi, and Y.-B. Shi Thyroid Hormone-dependent Gene Expression Program for Xenopus Neural Development J. Biol. Chem., March 28, 1997; 272(13): 8179 - 8188. [Abstract] [Full Text] [PDF]

				T. Miyamoto, A. Kaneko, T. Kakizawa, H. Yajima, K. Kamijo, R. Sekine, K. Hiramatsu, Y. Nishii, T. Hashimoto, and K. Hashizume Inhibition of Peroxisome Proliferator Signaling Pathways by Thyroid Hormone Receptor. COMPETITIVE BINDING TO THE RESPONSE ELEMENT J. Biol. Chem., March 21, 1997; 272(12): 7752 - 7758. [Abstract] [Full Text] [PDF]

				T. Nagasawa, S. Suzuki, T. Takeda, and L. J. DeGroot Thyroid Hormone Receptor {beta}1 Expression in Developing Mouse Limbs and Face Endocrinology, March 1, 1997; 138(3): 1276 - 1281. [Abstract] [Full Text] [PDF]

				Y.-T. Ting, M. Bhat, R. Wong, and S.-y. Cheng Tissue-specific Stabilization of the Thyroid Hormone beta 1 Nuclear Receptor by Phosphorylation J. Biol. Chem., February 14, 1997; 272(7): 4129 - 4134. [Abstract] [Full Text] [PDF]

				C. Wrutniak, I. Cassar-Malek, S. Marchal, A. Rascle, S. Heusser, J.-M. Keller, J. Fléchon, M. Daua, J. Samarut, J. Ghysdael, et al. A 43-kDa Protein Related to c-Erb A [IMAGE]1 Is Located in the Mitochondrial Matrix of Rat Liver J. Biol. Chem., July 7, 1995; 270(27): 16347 - 16354. [Abstract] [Full Text] [PDF]