| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 4, 2004
Accepted on October 15, 2004
Department of Medicine (L.C.M., S.R.), Pediatrics (S.R.) and Human Genetics (A.M.D.), Committees on Genetics and Molecular Medicine (S.R.) The University of Chicago, Chicago, IL and Cancer Genetics Branch (R.L.W., P.S.M.), National Human Genome Research Institute, NIH, Bethesda, MD
* To whom correspondence should be addressed.
SAMUEL REFETOFF, E-mail: refetoff{at}uchicago.edu
Human skin fibroblasts are readily accessible cells for propagation in culture without transformation, that can serve for direct pathophysiology studies in subjects with inherited diseases. We thus examined by quantitative fluorescent cDNA microarray analysis the effect of thyroid hormone (TH) on the expression of over 15,000 genes in fibroblasts of two normal individuals. Fibroblasts from two subjects with resistance to thyroid hormone (RTH) due to mutations in the TH receptor (TR) 
gene were used to confirm the specificity of the hormonal effect by the ability to discriminate between normal cells and cells with a defect in TH action. Microarray analysis identified 148 genes induced by 
1.4-fold and 5 genes repressed to 
0.7, 24 h after treatment with 2x10-9M T3. Taking into account duplicate genes these represented 91 upregulated and 5 downregulated genes, respectively. Confirmation by real-time PCR was obtained in 8 of 10 induced and 2 of 3 repressed genes that were tested. Further evidence for T3 specific induction was provided by a graded dose response absent in fibroblasts from the patients with RTH. The following genes not previously known to be induced by TH were identified and validated: AKR1 C1-3, COL6A3, RAB3B, PFKP, HIF-1
and ENO1. These genes as well as three known to be TH regulated in other species and found in this study also in human cells (GLUT1, SLC16A3 and BTEB1) have a variety of regulatory functions in development and metabolism. TH seems to induce these genes by initiating either genomic or non-genomic mechanisms. Surprisingly, TH-mediated downregulation of FGF7 and ADH1B persisted in fibroblasts from patients with RTH.
This first systematic study of TH-mediated gene expression in normal human cells identifies several new TH-responsive genes and demonstrates that skin fibroblasts are suitable for the study of TH action in health and in disease.
This article has been cited by other articles:
 |
|
 |
|
  T. Ueda, E. Compe, P. Catez, K. H. Kraemer, and J.-M. Egly Both XPD alleles contribute to the phenotype of compound heterozygote xeroderma pigmentosum patients J. Exp. Med., November 23, 2009; (2009) jem.20091892v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. E. Visser, K. A. Heemstra, S. M. A. Swagemakers, Z. Ozgur, E. P. Corssmit, J. Burggraaf, W. F. J. van Ijcken, P. J. van der Spek, J. W. A. Smit, and T. J. Visser Physiological Thyroid Hormone Levels Regulate Numerous Skeletal Muscle Transcripts J. Clin. Endocrinol. Metab., September 1, 2009; 94(9): 3487 - 3496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ohguchi, T. Tanaka, A. Uchida, K. Magoori, H. Kudo, I. Kim, K. Daigo, I. Sakakibara, M. Okamura, H. Harigae, et al. Hepatocyte Nuclear Factor 4{alpha} Contributes to Thyroid Hormone Homeostasis by Cooperatively Regulating the Type 1 Iodothyronine Deiodinase Gene with GATA4 and Kruppel-Like Transcription Factor 9 Mol. Cell. Biol., June 15, 2008; 28(12): 3917 - 3931. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Quignodon, C. Grijota-Martinez, E. Compe, R. Guyot, N. Allioli, D. Laperriere, R. Walker, P. Meltzer, S. Mader, J. Samarut, et al. A combined approach identifies a limited number of new thyroid hormone target genes in post-natal mouse cerebellum J. Mol. Endocrinol., July 1, 2007; 39(1): 17 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Flamant, K. Gauthier, and J. Samarut Thyroid Hormones Signaling Is Getting More Complex: STORMs Are Coming Mol. Endocrinol., February 1, 2007; 21(2): 321 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Rae, O. Gubbay, A. Kostogiannou, D. Price, H. O. D. Critchley, and S. G. Hillier Thyroid Hormone Signaling in Human Ovarian Surface Epithelial Cells J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 322 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Y. Wu, R. N. Cohen, E. Simsek, D. A. Senses, N. E. Yar, H. Grasberger, J. Noel, S. Refetoff, and R. E. Weiss A Novel Thyroid Hormone Receptor-{beta} Mutation That Fails to Bind Nuclear Receptor Corepressor in a Patient as an Apparent Cause of Severe, Predominantly Pituitary Resistance to Thyroid Hormone J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1887 - 1895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liu, X. Xia, J. D. Fondell, and P. M. Yen Thyroid Hormone-Regulated Target Genes Have Distinct Patterns of Coactivator Recruitment and Histone Acetylation Mol. Endocrinol., March 1, 2006; 20(3): 483 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Conrad, Y. Zhang, A. R. Walker, L. A. Olberding, A. Hanzlick, A. J. Zimmer, R. Morffi, and G. W. Conrad Thyroxine Affects Expression of KSPG-Related Genes, the Carbonic Anhydrase II Gene, and KS Sulfation in the Embryonic Chicken Cornea Invest. Ophthalmol. Vis. Sci., January 1, 2006; 47(1): 120 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Moeller, A. M. Dumitrescu, and S. Refetoff Cytosolic Action of Thyroid Hormone Leads to Induction of Hypoxia-Inducible Factor-1{alpha} and Glycolytic Genes Mol. Endocrinol., December 1, 2005; 19(12): 2955 - 2963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. R. Moore and R. K. Guy Coregulator Interactions with the Thyroid Hormone Receptor Mol. Cell. Proteomics, April 1, 2005; 4(4): 475 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Yen Studying Hormonal Regulation by Microarrays: Distinguishing the Trees from the Forest J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1241 - 1242. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
