甲状腺ホルモンの作用機構の解析

甲状腺ホルモン受容体と転写共役因子-甲状腺ホルモン不応症、甲状腺ホルモン結合蛋白などに関して、私達の研究の過程を振り返るともっとも多くの発表[1-10]を行ってきた分野です。

現在は別項に示す我々が同定した甲状腺ホルモン応答性遺伝子であるZAKI-4遺伝子のノックアウトマウスの解析を進めるとともに、神経系における甲状腺ホルモンの作用に注目して研究を進めています。

 

[1] Y. Takeuchi, Y. Murata, P. Sadow, Y. Hayashi, H. Seo, J. Xu, B. W. O'Malley, R. E. Weiss, and S. Refetoff, Steroid receptor coactivator-1 deficiency causes variable alterations in the modulation of T(3)-regulated transcription of genes in vivo, Endocrinology 143 (2002) 1346-1352.

[2] M. Rogatcheva, Y. Hayashi, S. Oda, H. Seo, K. Cua, S. Refetoff, M. Murakami, M. Mori, and Y. Murata, Type 1 iodothyronine deiodinase in the house musk shrew (Suncus murinus, Insectivora: Soricidae): cloning and characterization of complementary DNA, unique tissue distribution and regulation by T(3), Gen Comp Endocrinol 127 (2002) 48.

[3] P. E. Macchia, Y. Takeuchi, T. Kawai, K. Cua, K. Gauthier, O. Chassande, H. Seo, Y. Hayashi, J. Samarut, Y. Murata, R. E. Weiss, and S. Refetoff, Increased sensitivity to thyroid hormone in mice with complete deficiency of thyroid hormone receptor alpha, Proc Natl Acad Sci U S A 98 (2001) 349-354.

[4] S. Yamaguchi, Y. Murata, T. Nagaya, Y. Hayashi, S. Ohmori, Y. Nimura, and H. Seo, Glucocorticoids increase retinoid-X receptor alpha (RXRalpha) expression and enhance thyroid hormone action in primary cultured rat hepatocytes, J Mol Endocrinol 22 (1999) 81-90.

[5] M. Menjo, S. Yamaguchi, Y. Murata, Y. Hayashi, T. Nagaya, S. Ohmori, S. Refetoff, and H. Seo, Responsiveness to thyroid hormone is enhanced in rat hepatocytes cultured as spheroids compared with that in monolayers: altered responsiveness to thyroid hormone possibly involves complex formed on thyroid hormone response elements, Thyroid 9 (1999) 959-967.

[6] Y. Hayashi, D. Mangoura, and S. Refetoff, A mouse model of resistance to thyroid hormone produced by somatic gene transfer of a mutant thyroid hormone receptor, Mol Endocrinol 10 (1996) 100-106.

[7] T. Sunthornthepvarakul, M. E. Gottschalk, Y. Hayashi, and S. Refetoff, Brief report: resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene, N Engl J Med 332 (1995) 155-160.

[8] Y. Hayashi, T. Sunthornthepvarakul, and S. Refetoff, Mutations of CpG dinucleotides located in the triiodothyronine (T3)-binding domain of the thyroid hormone receptor (TR) beta gene that appears to be devoid of natural mutations may not be detected because they are unlikely to produce the clinical phenotype of resistance to thyroid hormone, J Clin Invest 94 (1994) 607-615.

[9] Y. Hayashi, A. M. DePaoli, C. F. Burant, and S. Refetoff, Expression of a thyroid hormone-responsive recombinant gene introduced into adult mice livers by replication-defective adenovirus can be regulated by endogenous thyroid hormone receptor, J Biol Chem 269 (1994) 23872-23875.

[10] Y. Hayashi, Y. Mori, O. E. Janssen, T. Sunthornthepvarakul, R. E. Weiss, K. Takeda, M. Weinberg, H. Seo, G. I. Bell, and S. Refetoff, Human thyroxine-binding globulin gene: complete sequence and transcriptional regulation, Mol Endocrinol 7 (1993) 1049-1060.

 

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