Abstract
In the vertebrate brain, the thalamus serves as a relay and integration station for diverse neuronal information en route from the periphery to the cortex. Deficiency of TH during development results in severe cerebral abnormalities similar to those seen in the mouse when the retinoic acid receptor (ROR)α gene is disrupted. To investigate the effect of the thyroid hormone receptors (TRs) on RORα gene expression, we used intact male mice, in which the genes encoding the α and β TRs have been deleted. In situ hybridization for RORα mRNA revealed that this gene is expressed in specific areas of the brain including the thalamus, pons, cerebellum, cortex, and hippocampus. Our quantitative data showed differences in RORα mRNA expression in different subthalamic nuclei between wild-type and knockout mice. For example, the centromedial nucleus of the thalamus, which plays a role in mediating nociceptive and visceral information from the brainstem to the basal ganglia and cortical regions, has less expression of RORα mRNA in the knockout mice (−37%) compared to the wild-type controls. Also, in the dorsal geniculate (+72%) and lateral posterior nuclei (+58%) we found more RORα mRNA in dKO as compared to dWT animals. Such differences in RORα mRNA expression may play a role in the behavioral alterations resulting from congenital hypothyroidism.
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Oppenheimer, J. H., Schwartz, H. L., and Strait, K. A. (1995). In: Molecular endocrinology: basic concepts and clincal correlations. Weintraub, B. (ed.). Raven Press: New York.
Lazar, M. (1993). Endocrine Rev. 14, 184–193.
Zhang, J. and Lazar, M. A. (2000). Annu. Rev. Physiol. 62, 439–466.
Sap, J., Munoz, A., Schmitt, J., Stunnenberg, H., and Vennstrom, B. (1989). Nature 340, 242–244.
Evans, R. M. (1988). Science 240, 889–895.
Mangelsdorf, D. J., Thummel, C., Beato, M., et al. (1995). Cell 83, 835–840.
Damm, K., Thompson, C. C., and Evans, R. M. (1989). Nature 339, 593–597.
Feng, X., Jiang, Y., Meltzer, P., and Yen, P. M. (2000). Mol. Endocrinol. 14, 947–955.
Flores-Morales, A., Gullberg, H., Fernandez, L., et al. (2002). Mol. Endocrinol. 16, 1257–1268.
Chin, W. W. (1991). In: Nuclear hormone receptors. Parker, M. (ed.). Academic Press: New York.
Harvey, C. B. and Williams, G. R. (2002). Thyroid 12, 441–446.
Delange, F. M. and Ermans, A. M. (1979). In: The thyroid: physiology and treatment of disease. Hershman, J. M. and Bray, G. A. (eds.). Pergamon Press: New York.
Bernal, J., Guadano-Ferraz, A., and Morte, B. (2003). Thyroid 13, 1005–1012.
Morreale de Escobar, G., Obregon, M. J., and Escobar del Rey, F. (2004). Eur. J. Endocrinol. 151(Suppl 3), U25-U37.
Forrest, D. (2004). Endocrinology 145, 4034–4036.
Anderson, G. W., Schoonover, C. M., and Jones, S. A. (2003). Thyroid 13, 1039–1056.
Konig, S. and Moura Neto, V. (2002). Cell Mol. Neurobiol. 22, 517–544.
Morte, B., Manzano, J., Scanlan, T. S., Vennstrom, B., and Bernal, J. (2004). Endocrinology 145, 1386–1391.
Morte, B., Manzano, J., Scanlan, T., Vennstrom, B., and Bernal, J. (2002). Proc. Natl. Acad. Sci. USA 99, 3985–3989.
Heuer, H. and Mason, C. A. (2003). J. Neurosci. 23, 10604–10612.
Koibuchi, N. and Chin, W. W. (2000). Trends Endocrinol. Metab. 11, 123–128.
Legrand, J. and Bout, M. C. (1970). C. R. Acad. Sci. Hebd. Seances. Acad. Sci. D. 271, 1199–1202.
Sidman, R. L., Lane, P. W., and Dickie, M. M. (1962). Science 137, 610–612.
Clos, J., Crepel, F., Legrand, C., Legrand, J., Rabie, A., and Vigouroux, E. (1974). Gen. Comp. Endocrinol. 23, 178–192.
Crepel, F. (1974). Exp. Brain Res. 20, 403–420.
Crepel, F. (1975). Brain Res. 85, 157–160.
Nicholson, J. L. and Altman, J. (1972). Science 176,
Nicholson, J. L. and Altman, J. (1972). Brain Res. 44, 13–23.
Rabie, A., Favre, C., Clavel, M. C., and Legrand, J. (1979). Brain Res. 161, 469–479.
Herrup, K. (1983). Dev. Brain Res. 11, 267–274.
Sotelo, C. and Changeux, J.-P. (1974). Brain Res. 67, 519–526.
Hamilton, B. A., Frankel, W. N., Kerrebrock, A. W., et al. (1996). Nature 379, 736–739.
Dussault, I., Fawcett, D., Matthyssen, A., Bader, J. A., and Giguere, V. (1998). Mech. Dev. 70, 147–153.
Giguere, V., Tini, M., Flock, G., Ong, E., Evans, R. M., and Otulakowski, G. G. (1994). Genes Dev. 8, 538–553.
Matsui, T., Sashihara, S., Oh, Y., and Waxman, S. G. (1995). Brain Res. Mol. Brain Res. 33, 217–226.
Jetten, A. M., Kurebayashi, S., and Ueda, E. (2001). Prog. Nucleic Acid Res. Mol. Biol. 69, 205–247.
Sashihara, S., Felts, P. A., Waxman, S. G., and Matsui, T. (1996). Brain Res. Mol. Brain Res. 42, 109–117.
Matysiak-Scholze, U. and Nehls, M. (1997). Genomics 43, 78–84.
Matsui, T. (1997). Genes Cells 2, 263–272.
Oppenheimer, J. H. and Schwartz, H. L. (1997). Endocr. Rev. 18, 462–475.
Zou, L., Hagen, S. G., Strait, K. A., and Oppenheimer, J. H. (1994). J. Biol. Chem. 269, 13346–13352.
Chu, K. and Zingg, H. H. (1999). J. Mol. Endocrinol. 23, 337–346.
Matsui, T. (1996). Biochem. Biophys. Res. Commun. 220, 405–410.
Koibuchi, N and Chin, W. W. (1998). Endocrinology 139, 2335–2341.
Kandel, E. R., Schwartz, J. H., and Jessel, T. M. (1991). Principles of neural science. Elsevier: New York.
Bauer, M. S. and Whybrow, P. C. (1988). Integr. Psychiatry 6, 75–100.
Arque, J. M., Segura, R., and Torrubia, R. (1987). Neuropsychobiology 18, 127–133.
Balada, F., Torrubia, R., and Arque, J. M. (1992). Neuropsychobiology 25, 208–213.
Koibuchi, N., Yamaoka, S., and Chin, W. W. (2001). Thyroid 11, 205–210.
Barradas, P. C., Vieira, R. S., and De Freitas, M. S. (2001). J. Neurosci. Res. 66, 254–261.
Ng, L., Hurley, J. B., Dierks, B., et al. (2001). Nat. Genet. 27, 94–98.
Göthe, S., Wang, Z., Ng, L., et al. (1999). Genes Develop. 13, 1329–1341.
Forrest, D., Erway, L. C., Ng, L., Altschuler, R., and Curran, T. (1996). Nat. Genet. 13, 354–357.
Kia, H. K., Krebs, C. J., Koibuchi, N., Chin, W. W., and Pfaff, D. W. (2001). J. Comp. Neurol. 437, 286–295.
Mize, A. L. and Alper, R. H. (2000). Brain Res. 859, 326–333.
Franklin, K. B. J. and Paxinos, G. (1997). The mouse brain in stereotaxic coordinates. Academic Press: San Diego, CA.
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Vasudevan, N., Kia, H.K., Hadjimarkou, M. et al. Retinoid-related receptor (ROR) α mRNA expression is altered in the brain of male mice lacking all ligand-binding thyroid hormone receptor (TR) isoforms. Endocr 26, 25–32 (2005). https://doi.org/10.1385/ENDO:26:1:025
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DOI: https://doi.org/10.1385/ENDO:26:1:025