| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Thyroid Division (B.G., J.W.H., H.M.T., P.R.L.) Department of
Medicine Brigham and Women’s Hospital Harvard Medical
School Boston, Massachusetts 02115
Dipartimento di
Endocrinologia ed Oncologia Molecolare e Clinica (D.S.)
Università degli Studi di Napoli "Federico II" Napoli,
Italy 80131
Types 1 and 2 iodothyronine deiodinases (D1 and D2) catalyze the production of T3 from T4. D2 mRNA is abundant in the human thyroid but very low in adult rat thyroid, whereas D1 activity is high in both. To understand the molecular regulation of these genes in thyroid cells, the effect of thyroid transcription factor 1 (TTF-1) and the paired domain-containing protein 8 (Pax-8) on the transcriptional activity of the deiodinase promoters were studied. Both the approximately 6.5-kb hdio2 sequence and its most 3' 633 bp were activated 10-fold by transiently expressed TTF-1 in COS-7 cells, but the hdio1 was unaffected. Surprisingly, the response of the rdio2 gene to TTF-1 was only 3-fold despite the 73% identity with the proximal 633-bp region of hdio2 including complete conservation of a functional cAMP response element at -90. Neither human nor rat dio2 nor human dio1 was induced by Pax-8. The binding affinity of four putative TTF-1 binding sites in hdio2 were compared by a semiquantitative gel retardation assay using in vitro expressed TTF-1 homeodomain protein. Only two sites, D and C1 (both of which are absent in rdio2), had significant affinity. Functional analyses showed that both sites are required for the full response to TTF-1. These results can explain the differential expression of dio2 in thyroid and potentially other tissues in humans and rats.
This article has been cited by other articles:
 |
|
 |
|
  G. Canettieri, A. Franchi, M. D. Guardia, I. Morantte, M. G. Santaguida, J. W. Harney, P. R. Larsen, and M. Centanni Activation of Thyroid Hormone Is Transcriptionally Regulated by Epidermal Growth Factor in Human Placenta-Derived JEG3 Cells Endocrinology, February 1, 2008; 149(2): 695 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Chik, M. T. Wloka, D. M. Price, and A. K. Ho The Role of Repressor Proteins in the Adrenergic Induction of Type II Iodothyronine Deiodinase in Rat Pinealocytes Endocrinology, July 1, 2007; 148(7): 3523 - 3531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zeold, M. Doleschall, M. C. Haffner, L. P. Capelo, J. Menyhert, Z. Liposits, W. S. da Silva, A. C. Bianco, I. Kacskovics, C. Fekete, et al. Characterization of the Nuclear Factor-{kappa}B Responsiveness of the Human dio2 Gene Endocrinology, September 1, 2006; 147(9): 4419 - 4429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Dentice, V. Cordeddu, A. Rosica, A. M. Ferrara, L. Santarpia, D. Salvatore, L. Chiovato, A. Perri, L. Moschini, C. Fazzini, et al. Missense Mutation in the Transcription Factor NKX2-5: A Novel Molecular Event in the Pathogenesis of Thyroid Dysgenesis J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1428 - 1433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kohrle, F. Jakob, B. Contempre, and J. E. Dumont Selenium, the Thyroid, and the Endocrine System Endocr. Rev., December 1, 2005; 26(7): 944 - 984. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Dentice, C. Luongo, A. Elefante, R. Ambrosio, S. Salzano, M. Zannini, R. Nitsch, R. Di Lauro, G. Rossi, G. Fenzi, et al. Pendrin Is a Novel In Vivo Downstream Target Gene of the TTF-1/Nkx-2.1 Homeodomain Transcription Factor in Differentiated Thyroid Cells Mol. Cell. Biol., November 15, 2005; 25(22): 10171 - 10182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. W. J. S. Wassen, W. Klootwijk, E. Kaptein, D. J. Duncker, T. J. Visser, and G. G. J. M. Kuiper Characteristics and Thyroid State-Dependent Regulation of Iodothyronine Deiodinases in Pigs Endocrinology, September 1, 2004; 145(9): 4251 - 4263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Fekete, B. Gereben, M. Doleschall, J. W. Harney, J. M. Dora, A. C. Bianco, S. Sarkar, Z. Liposits, W. Rand, C. Emerson, et al. Lipopolysaccharide Induces Type 2 Iodothyronine Deiodinase in the Mediobasal Hypothalamus: Implications for the Nonthyroidal Illness Syndrome Endocrinology, April 1, 2004; 145(4): 1649 - 1655. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Moeller, S. Kimura, T. Kusakabe, X.-H. Liao, J. Van Sande, and S. Refetoff Hypothyroidism in Thyroid Transcription Factor 1 Haploinsufficiency Is Caused by Reduced Expression of the Thyroid-Stimulating Hormone Receptor Mol. Endocrinol., November 1, 2003; 17(11): 2295 - 2302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dentice, C. Morisco, M. Vitale, G. Rossi, G. Fenzi, and D. Salvatore The Different Cardiac Expression of the Type 2 Iodothyronine Deiodinase Gene between Human and Rat Is Related to the Differential Response of the dio2 Genes to Nkx-2.5 and GATA-4 Transcription Factors Mol. Endocrinol., August 1, 2003; 17(8): 1508 - 1521. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-H. Wang, R. Chmelik, and M. Nirenberg Sequence-specific DNA binding by the vnd/NK-2 homeodomain of Drosophila PNAS, October 1, 2002; 99(20): 12721 - 12726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Gereben, A. Kollar, J. W. Harney, and P. R. Larsen The mRNA Structure Has Potent Regulatory Effects on Type 2 Iodothyronine Deiodinase Expression Mol. Endocrinol., July 1, 2002; 16(7): 1667 - 1679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Bianco, D. Salvatore, B. Gereben, M. J. Berry, and P. R. Larsen Biochemistry, Cellular and Molecular Biology, and Physiological Roles of the Iodothyronine Selenodeiodinases Endocr. Rev., February 1, 2002; 23(1): 38 - 89. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
