Endocrinology, Vol 137, 1032-1041, Copyright © 1996 by Endocrine Society

ARTICLES

Cell-specific effects of thyroid hormone on RC3/neurogranin expression in rat brain

MA Iniguez, L De Lecea, A Guadano-Ferraz, B Morte, D Gerendasy, JG Sutcliffe and J Bernal
Instituto de Investigaciones Biomedicas, Madrid, Spain.

To identify thyroid hormone-sensitive neuronal populations in the forebrain, we studied the effects of thyroid hormone deficiency and replacement on the expression of RC3 messenger RNA (mRNA) in the rat brain by in situ hybridization. RC3/neurogranin is a brain-specific, calmodulin-binding, protein kinase C substrate that has been implicated in postsynaptic events involving calcium as a second messenger. We have previously shown that RC3 mRNA and protein concentrations are thyroid hormone dependent in developing and adult rats. In normal developing rats, RC3 expression occurs in two phases. Before postnatal day 10 (P10), RC3 mRNA was detected mainly in layers II/III and V of cerebral cortex and the CA fields of the hippocampus. From P10 to P15, it decreased in layer V and increased in layer VI, the retrosplenial cortex, the caudate-putamen nucleus, and the dentate gyrus. Expression in the caudate followed a lateral to medial gradient. Thyroid hormone deficiency interfered with the late phase of RC3 expression, such that developing hypothyroid rats showed lower RC3 expression in layer VI, the retrosplenial cortex, the dentate gyrus, and the caudate, and increased expression in layer V. These changes were reverted by T4 treatment. Adult- onset hyperthyroidism also reversibly decreased hybridization in the striatum. In contrast to other molecular targets of thyroid hormone in the brain, such as myelin genes, expression of RC3 was also affected by long term hypothyroidism in the absence of hormone replacement, indicating that thyroid hormone is a required factor for the cell-specific control of RC3 expression. In addition to identifying thyroid hormone-sensitive neurons, our results suggest that one action of thyroid hormone during brain development is the timely coordination of gene expression among phenotypically different, region- specific neuronal populations.

This article has been cited by other articles:

				R. Bansal and R. T. Zoeller Polychlorinated Biphenyls (Aroclor 1254) Do Not Uniformly Produce Agonist Actions on Thyroid Hormone Responses in the Developing Rat Brain Endocrinology, August 1, 2008; 149(8): 4001 - 4008. [Abstract] [Full Text] [PDF]

				M. R. Roberts, M. Srinivas, D. Forrest, G. Morreale de Escobar, and T. A. Reh Making the gradient: Thyroid hormone regulates cone opsin expression in the developing mouse retina PNAS, April 18, 2006; 103(16): 6218 - 6223. [Abstract] [Full Text] [PDF]

				M. B Zimmermann, K. Connolly, M. Bozo, J. Bridson, F. Rohner, and L. Grimci Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study Am. J. Clinical Nutrition, January 1, 2006; 83(1): 108 - 114. [Abstract] [Full Text] [PDF]

				L. Sui, W. L. Anderson, and M. E. Gilbert Impairment in Short-Term but Enhanced Long-Term Synaptic Potentiation and ERK Activation in Adult Hippocampal Area CA1 Following Developmental Thyroid Hormone Insufficiency* Toxicol. Sci., May 1, 2005; 85(1): 647 - 656. [Abstract] [Full Text] [PDF]

				R. T. Zoeller, R. Bansal, and C. Parris Bisphenol-A, an Environmental Contaminant that Acts as a Thyroid Hormone Receptor Antagonist in Vitro, Increases Serum Thyroxine, and Alters RC3/Neurogranin Expression in the Developing Rat Brain Endocrinology, February 1, 2005; 146(2): 607 - 612. [Abstract] [Full Text] [PDF]

				K.-P. Huang, F. L. Huang, T. Jager, J. Li, K. G. Reymann, and D. Balschun Neurogranin/RC3 Enhances Long-Term Potentiation and Learning by Promoting Calcium-Mediated Signaling J. Neurosci., November 24, 2004; 24(47): 10660 - 10669. [Abstract] [Full Text] [PDF]

				C. S. Roegge, V. C. Wang, B. E. Powers, A. Y. Klintsova, S. Villareal, W. T. Greenough, and S. L. Schantz Motor Impairment in Rats Exposed to PCBs and Methylmercury during Early Development Toxicol. Sci., February 1, 2004; 77(2): 315 - 324. [Abstract] [Full Text] [PDF]

				J. Manzano, B. Morte, T. S. Scanlan, and J. Bernal Differential Effects of Triiodothyronine and the Thyroid Hormone Receptor {beta}-Specific Agonist GC-1 on Thyroid Hormone Target Genes in the Brain Endocrinology, December 1, 2003; 144(12): 5480 - 5487. [Abstract] [Full Text] [PDF]

				A. Montero-Pedrazuela, J. Bernal, and A. Guadano-Ferraz Divergent Expression of Type 2 Deiodinase and the Putative Thyroxine-Binding Protein p29, in Rat Brain, Suggests that They Are Functionally Unrelated Proteins Endocrinology, March 1, 2003; 144(3): 1045 - 1052. [Abstract] [Full Text] [PDF]

				B. Morte, J. Manzano, T. Scanlan, B. Vennstrom, and J. Bernal Deletion of the thyroid hormone receptor alpha 1 prevents the structural alterations of the cerebellum induced by hypothyroidism PNAS, March 19, 2002; 99(6): 3985 - 3989. [Abstract] [Full Text] [PDF]

				A. Siddiq, T. Miyazaki, Y. Takagishi, Y. Kanou, S. Hayasaka, M. Inouye, H. Seo, and Y. Murata Expression of ZAKI-4 Messenger Ribonucleic Acid in the Brain during Rat Development and the Effect of Hypothyroidism Endocrinology, May 1, 2001; 142(5): 1752 - 1759. [Abstract] [Full Text]

				J. Almeida Palha, R. Fernandes, G. Morreale de Escobar, V. Episkopou, M. Gottesman, and M. J. Saraiva Transthyretin Regulates Thyroid Hormone Levels in the Choroid Plexus, But Not in the Brain Parenchyma: Study in a Transthyretin-Null Mouse Model Endocrinology, September 1, 2000; 141(9): 3267 - 3272. [Abstract] [Full Text] [PDF]

				C. S. Roegge, B.-W. Seo, K. M. Crofton, and S. L. Schantz Gestational-Lactational Exposure to Aroclor 1254 Impairs Radial-Arm Maze Performance in Male Rats Toxicol. Sci., September 1, 2000; 57(1): 121 - 130. [Abstract] [Full Text] [PDF]

				A. Guadano-Ferraz, M. J. Escamez, E. Rausell, and J. Bernal Expression of Type 2 Iodothyronine Deiodinase in Hypothyroid Rat Brain Indicates an Important Role of Thyroid Hormone in the Development of Specific Primary Sensory Systems J. Neurosci., May 1, 1999; 19(9): 3430 - 3439. [Abstract] [Full Text] [PDF]

				C. M. de Arrieta, B. Morte, A. Coloma, and J. Bernal The Human RC3 Gene Homolog, NRGN Contains a Thyroid Hormone-Responsive Element Located in the First Intron Endocrinology, January 1, 1999; 140(1): 335 - 343. [Abstract] [Full Text]

				A. Guadano-Ferraz, M. J. Obregon, D. L. St. Germain, and J. Bernal The type 2 iodothyronine deiodinase is expressed primarily in glial cells in the neonatal rat brain PNAS, September 16, 1997; 94(19): 10391 - 10396. [Abstract] [Full Text] [PDF]