Abstract
Transthyretin (TTR) is an extracellular thyroid hormone (TH) distributor protein. The TH distributor proteins ensure the adequate distribution of THs throughout the body, buffer against excess TH uptake into cells and maintain an extrathyroidal reserve of THs that may protect against TH deficiency when TH demand is increased. Thyroid hormones are vital for normal postnatal development. Thus, the postnatal development and growth of tissues responsive to THs has been investigated in TTR null mice. Although the developmental surge in plasma T4 concentrations was evident in 2-week-old TTR null mice, total and free T4 in the plasma were significantly reduced. Characteristics of the developing TTR null mice included delayed suckling-to-weaning transition, delayed onset of growth and retarded longitudinal bone growth. In addition, ileums from newborn TTR null mice displayed disordered cellular structure and contained fewer goblet cells. Although TH homeostasis within the brain of the developing TTR null mice did not appear to be compromised, subtle differences suggested a degree of immaturity in the developing brain, such as higher protein concentrations of cerebrospinal fluid from newborn and 2-week-old TTR null mice than in age-matched wild type mice. Collectively, these studies demonstrate the importance of TTR during post-natal development and suggest that the development of the central nervous system is essentially preserved at the expense of peripheral tissues in TTR null mice.
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Abbreviations
- CNS:
-
Central nervous system
- CSF:
-
cerebrospinal fluid
- D1:
-
Type 1 deiodinase
- D2:
-
Type 2 deiodinase
- T3 :
-
3′,3,5-triiodo-l-thyronine
- T4 :
-
3′,5′,3,5-tetraiodo-l-thyronine
- TBG:
-
Thyroxine-binding globulin
- TH:
-
Thyroid hormone
- TR:
-
Thyroid hormone receptor
- TTR:
-
Transthyretin
References
Althausen TL (1949) Hormonal and vitamin factors in intestinal absorption. Gastroenterology 12:467–480
Anderson GW (2001) Thyroid hormones and the brain. Front Neuroendocrinol 22:1–17
Baran D (1996) The skeletal system in hypothyroidism. In: Braverman L, Utiger R (eds) Werner and Ingbar's The Thyroid. A Fundamental and Clinical Text, 7th edn. Lipincott-Raven, Philadelphia
Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR (2002) Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev 23:38–89
Blázquez E, Sugase T, Blázquez M, Foá PP (1974) Neonatal changes in the concentration of rat liver cyclic AMP and of serum glucose, free fatty acids, insulin, pancreatic, and total glucagon in man and in the rat. J Lab Clin Med 83:957–967
Buaboocha W, Gemmell RT (1995) Thyroid gland development in the brushtail possum, Trichosurus vulpecula. Anat Rec 243:254–260
Chan S, Kachilele S, McCabe CJ, Tannahill LA, Boelaert K, Gittoes NJ, Visser TJ, Franklyn JA, Kilby MD (2002) Early expression of thyroid hormone deiodinases and receptors in human fetal cerebral cortex. Brain Res Dev Brain Res 138:109–116
Darras VM, Visser TJ, Berghman LR, Kuhn ER (1992) Ontogeny of type I and type III deiodinase activities in embryonic and posthatch chicks: relationship with changes in plasma triiodothyronine and growth hormone levels. Comp Biochem Physiol Comp Physiol 103:131–136
de Jesus EG, Hirano T, Inui Y (1991) Changes in cortisol and thyroid hormone concentrations during early development and metamorphosis in the Japanese flounder, Paralichthys olivaceus. Gen Comp Endocrinol 82:369–376
DeLong G (1996) The neuromuscular system and brain in hypothyroidism. In: Braverman L, Utiger R (eds) Werner and Ingbar's The thyroid. A fundamental and clinical text, 7th edn. Lippincott-Raven, Philadelphia, pp 826–835
Dickson P, Aldred A, Menting J, Marley P, Sawyer W, Schreiber G (1987) Thyroxine transport in choroid plexus. J Biol Chem 262:13907–13915
Dickson PW, Aldred AR, Marley PD, Bannister D, Schreiber G (1986) Rat choroid plexus specializes in the synthesis and the secretion of transthyretin (prealbumin). Regulation of transthyretin synthesis in choroid plexus is independent from that in liver. J Biol Chem 261:3475–3478
Dickson PW, Schreiber G (1986) High levels of messenger RNA for transthyretin (prealbumin) in human choroid plexus. Neurosci Lett 66:311–315
Dziegielewska KM, Knott GW, Saunders NR (2000) The nature and composition of the internal environment of the developing brain. Cell Mol Neurobiol 20:41–56
Fraichard A, Chassande O, Plateroti M, Roux JP, Trouillas J, Dehay C, Legrand C, Gauthier K, Kedinger M, Malaval L, Rousset B, Samarut J (1997) The T3R alpha gene encoding a thyroid hormone receptor is essential for post-natal development and thyroid hormone production. EMBO J 16:4412–4420
Fung WP, Thomas T, Dickson PW, Aldred AR, Milland J, Dziadek M, Power B, Hudson P, Schreiber G (1988) Structure and expression of the rat transthyretin (prealbumin) gene. J Biol Chem 263:480–488
Funkenstein B, Perrot V, Brown CL (1999) Cloning of putative piscine (Sparus aurata) transthyretin: developmental expression and tissue distribution. Mol Cell Endocrinol 157:67–73
Galton VA, McCarthy PT, St Germain DL (1991) The ontogeny of iodothyronine deiodinase systems in liver and intestine of the rat. Endocrinology 128:1717–1722
Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N (1999) VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5:623–628
Girard J, Ferre P, Pegorier JP, Duee PH (1992) Adaptations of glucose and fatty acid metabolism during perinatal period and suckling–weaning transition. Physiol Rev 72:507–562
Goodridge AG, Klautky SA, Fantozzi DA, Baillie RA, Hodnett DW, Chen W, Thurmond DC, Xu G, Roncero C (1996) Nutritional and hormonal regulation of expression of the gene for malic enzyme. Prog Nucleic Acid Res Mol Biol 52:89–122
Gross J, Leblond CP, Franklin AE, Quastel JH (1950) Presence of iodinated amino acids in unhydrolyzed thyroid and plasma. Science 111:605–608
Gross J, Pitt-Rivers R (1953) 3:5:3′-Triiodothyronine. I. Isolation from thyroid gland and synthesis. Biochem J 53:645–650
Hadj-Sahraoui N, Seugnet I, Ghorbel MT, Demeneix B (2000) Hypothyroidism prolongs mitotic activity in the post-natal mouse brain. Neurosci Lett 280:79–82
Henning SJ (1981) Postnatal development: coordination of feeding, digestion, and metabolism. Am J Physiol 241:G199–G214
Hodin RA, Chamberlain SM, Upton MP (1992) Thyroid hormone differentially regulates rat intestinal brush border enzyme gene expression. Gastroenterology 103:1529–1536
Hodin RA, Meng S, Chamberlain SM (1994) Thyroid hormone responsiveness is developmentally regulated in the rat small intestine: a possible role for the alpha-2 receptor variant. Endocrinology 135:564–568
Howell D, Dean D (1992) The biology, chemistry, and biochemistry of the mammalian growth plate. In: Coe F, Favus M (eds) Disorders of Bone and Mineral Metabolism. Raven Press, New York, pp 313–353
Hulbert AJ (2000) Thyroid hormones and their effects: a new perspective. Biol Rev Camb Philos Soc 75:519–631
Ishii H, Inada M, Tanaka K, Mashio Y, Naito K, Nishikawa M, Imura H (1981) Triiodothyronine generation from thyroxine in human thyroid: enhanced conversion in Graves' thyroid tissue. J Clin Endocrinol Metab 52:1211–1217
Israel EJ, Pang KY, Harmatz PR, Walker WA (1987) Structural and functional maturation of rat gastrointestinal barrier with thyroxine. Am J Physiol 252:G762–G767
Janssens PA, Grigg JA, Dove H, Hulbert AJ (1990) Thyroid hormones during development of a marsupial, the tammar wallaby, Macropus eugenii. J Endocrinol 127:427–436
Kaplan MM, Yaskoski KA (1981) Maturational patterns of iodothyronine phenolic and tyrosyl ring deiodinase activities in rat cerebrum, cerebellum, and hypothalamus. J Clin Invest 67: 1208–1214
Kodding R, Fuhrmann H, von zur Muhlen A (1986) Investigations on iodothyronine deiodinase activity in the maturing rat brain. Endocrinology 118:1347–1352
Larsen PD, DeLallo L (1989) Cerebrospinal fluid transthyretin in the neonate and blood-cerebrospinal fluid barrier permeability. Ann Neurol 25:628–630
Larsen PR, Silva JE, Kaplan MM (1981) Relationships between circulating and intracellular thyroid hormones: physiological and clinical implications. Endocr Rev 2:87–102
Lemkine GF, Raj A, Alfama G, Turque N, Hassani Z, Alegria-Prevot O, Samarut J, Levi G, Demeneix BA (2005) Adult neural stem cell cycling in vivo requires thyroid hormone and its alpha receptor. FASEB J 19:863–865
Lewinson D, Harel Z, Shenzer P, Silbermann M, Hochberg Z (1989) Effect of thyroid hormone and growth hormone on recovery from hypothyroidism of epiphyseal growth plate cartilage and its adjacent bone. Endocrinology 124:937–945
Loughna S, Bennett P, Moore G (1995) Molecular analysis of the expression of transthyretin in intestine and liver from trisomy 18 fetuses. Hum Genet 95:89–95
Médaille C, Trumel C, Concordet D, Vergez F, Braun JP (2004) Comparison of plasma/serum urea and creatinine concentrations in the dog: a 5-year retrospective study in a commercial veterinary clinical pathology laboratory. J Vet Med A Physiol Pathol Clin Med 51:119–123
Mendel CM, Weisiger RA, Jones AL, Cavalieri RR (1987) Thyroid hormone-binding proteins in plasma facilitate uniform distribution of thyroxine within tissues: a perfused rat liver study. Endocrinology 120:1742–1749
Meyer D, Harvey J (2004) Veterinary Laboratory Medicine. Interpretation and Diagnosis, 3rd edn. Saunders, St. Louis, MO
Miura M, Tanaka K, Komatsu Y, Suda M, Yasoda A, Sakuma Y, Ozasa A, Nakao K (2002) Thyroid hormones promote chondrocyte differentiation in mouse ATDC5 cells and stimulate endochondral ossification in fetal mouse tibias through iodothyronine deiodinases in the growth plate. J Bone Miner Res 17:443–454
Miwa S, Inui Y (1987) Effects of various doses of thyroxine and triiodothyronine on the metamorphosis of flounder (Paralichthys olivaceus). Gen Comp Endocrinol 67:356–363
Molero C, Benito M, Lorenzo M (1993) Regulation of malic enzyme gene expression by nutrients, hormones, and growth factors in fetal hepatocyte primary cultures. J Cell Physiol 155:197–203
Mondou PM, Kaltenbach JC (1979) Thyroxine concentrations in blood serum and pericardial fluid of metamorphosing tadpoles and of adult frogs. Gen Comp Endocrinol 39:343–349
Monk JA (2006) Thyroid hormone homeostasis in developing and adult transthyretin null mice. PhD thesis, The University of Melbourne, Parkville, Australia
O'Shea PJ, Williams GR (2002) Insight into the physiological actions of thyroid hormone receptors from genetically modified mice. J Endocrinol 175:553–570
Palha JA, Fernandes R, de Escobar GM, Episkopou V, Gottesman M, Saraiva MJ (2000) Transthyretin regulates thyroid hormone levels in the choroid plexus, but not in the brain parenchyma: study in a transthyretin-null mouse model. Endocrinology 141:3267–3272
Palha JA, Hays MT, Morreale de Escobar G, Episkopou V, Gottesman ME, Saraiva MJ (1997) Transthyretin is not essential for thyroxine to reach the brain and other tissues in transthyretin-null mice. Am J Physiol 272:E485–E493
Pittman CS, Chambers JB, Jr., Read VH (1971) The extrathyroidal conversion rate of thyroxine to triiodothyronine in normal man. J Clin Invest 50:1187–1196
Richardson SJ, Aldred AR, Leng SL, Renfree MB, Hulbert AJ, Schreiber G (2002) Developmental profile of thyroid hormone distributor proteins in a marsupial, the tammar wallaby Macropus eugenii. Gen Comp Endocrinol 125:92–103
Richardson SJ, Lemkine GF, Alfama G, Hassani Z, Demeneix BA (2007) Cell division and apoptosis in the adult neural stem cell niche are differentially affected in transthyretin null mice. Neurosci Lett 421:234–238
Richardson SJ, Monk JA, Shepherdley CA, Ebbesson LO, Sin F, Power DM, Frappell PB, Kohrle J, Renfree MB (2005) Developmentally regulated thyroid hormone distributor proteins in marsupials, a reptile, and fish. Am J Physiol Regul Integr Comp Physiol 288:R1264–R1272
Robson H, Siebler T, Stevens DA, Shalet SM, Williams GR (2000) Thyroid hormone acts directly on growth plate chondrocytes to promote hypertrophic differentiation and inhibit clonal expansion and cell proliferation. Endocrinology 141:3887–3897
Rovet JF (1999) Congenital hypothyroidism: long-term outcome. Thyroid 9:741–748
Schreiber G, Aldred AR, Jaworowski A, Nilsson C, Achen M, Segal M (1990) Thyroxine transport from blood to brain via transthyretin synthesis in choroid plexus. Am J Physiol Regul Integr Comp Physiol 258: R338–R345
Schreiber G, Richardson SJ (1997) The evolution of gene expression, structure and function of transthyretin. Comp Biochem Physiol B Biochem Mol Biol 116:137–160
Shen S, Berry W, Jaques S, Pillai S, Zhu J (2004) Differential expression of iodothyronine deiodinase type 2 in growth plates of chickens divergently selected for incidence of tibial dyschondroplasia. Anim Genet 35:114–118
Shepherdley CA, Daniels CB, Orgeig S, Richardson SJ, Evans BK, Darras VM (2002) Glucocorticoids, thyroid hormones, and iodothyronine deiodinases in embryonic saltwater crocodiles. Am J Physiol Regul Integr Comp Physiol 283:R1155–R1163
Silva JE, Larsen PR (1982) Comparison of iodothyronine 5′-deiodinase and other thyroid-hormone-dependent enzyme activities in the cerebral cortex of hypothyroid neonatal rat. Evidence for adaptation to hypothyroidism. J Clin Invest 70:1110–1123
Song MK, Dozin B, Grieco D, Rall JE, Nikodem VM (1988) Transcriptional activation and stabilization of malic enzyme mRNA precursor by thyroid hormone. J Biol Chem 263: 17970–17974
Specker JL, DiStefano JJ, III, Grau EG, Nishioka RS, Bern HA (1984) Development-associated changes in thyroxine kinetics in juvenile salmon. Endocrinology 115:399–406
Stauder AJ, Dickson PW, Aldred AR, Schreiber G, Mendelsohn FA, Hudson P (1986) Synthesis of transthyretin (pre-albumin) mRNA in choroid plexus epithelial cells, localized by in situ hybridization in rat brain. J Histochem Cytochem 34:949–952
Stevens DA, Hasserjian RP, Robson H, Siebler T, Shalet SM, Williams GR (2000) Thyroid hormones regulate hypertrophic chondrocyte differentiation and expression of parathyroid hormone-related peptide and its receptor during endochondral bone formation. J Bone Miner Res 15:2431–2442
Suzuki S, Suzuki M (1981) Changes in thyroidal and plasma iodine compounds during and after metamorphosis of the bullfrog, Rana catesbeiana. Gen Comp Endocrinol 45:74–81
Taurog A, Evans ES (1967) Extrathyroidal thyroxine formation in completely thyroidectomized rats. Endocrinology 80:915–925
Thomas T, Schreiber G (1985) Acute-phase response of plasma protein synthesis during experimental inflammation in neonatal rats. Inflammation 9:1–7
Thommes RC, Hylka VW (1977) Plasma iodothyronines in the embryonic and immediate post-hatch chick. Gen Comp Endocrinol 32:417–422
Underwood L, Van Wyk J (1992) Normal and aberrant growth. In: William's Textbook of Endocrinology In: Wilson J, Foster D (eds) William's Textbook of Endocrinology 8th edn. W.B. Saunders Company, Philadelphia, pp 1079–1138
van Doorn J, Roelfsema F, van der Heide D (1982) Contribution from local conversion of thyroxine to 3,5,3′-triiodothyronine to intracellular 3,5,3′-triiodothyronine in several organs in hypothyroid rats at isotope equilibrium. Acta Endocrinol (Copenh) 101:386–396
van Doorn J, Roelfsema F, van der Heide D (1985) Concentrations of thyroxine and 3,5,3′-triiodothyronine at 34 different sites in euthyroid rats as determined by an isotopic equilibrium technique. Endocrinology 117:1201–1208
van Doorn J, van der Heide D, Roelfsema F (1983) Sources and quantity of 3,5,3′-triiodothyronine in several tissues of the rat. J Clin Invest 72:1778–1792
Vigouroux E, Clos J, Legrand J (1979) Uptake and metabolism of exogenous and endogenous thyroxine in the brain of young rats. Horm Metab Res 11:228–232
Vranckx R, Savu L, Maya M, Nunez EA (1990) Characterization of a major development-regulated serum thyroxine-binding globulin in the euthyroid mouse. Biochem J 271:373–379
Weber GM, Farrar ES, Tom CK, Grau EG (1994) Changes in whole-body thyroxine and triiodothyronine concentrations and total content during early development and metamorphosis of the toad Bufo marinus. Gen Comp Endocrinol 94:62–71
Wrutniak C, Cabello G, Bosc M (1985) Plasma free and total iodothyronine levels in hypophysectomized and intact lamb foetuses during the last third of gestation. Acta Endocrinol (Copenh) 110:388–394
Yen PM (2001) Physiological and molecular basis of thyroid hormone action. Physiol Rev 81:1097–1142
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Monk, J.A., Richardson, S.J. (2009). Transthyretin Null Mice: Developmental Phenotypes. In: Richardson, S.J., Cody, V. (eds) Recent Advances in Transthyretin Evolution, Structure and Biological Functions. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00646-3_18
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