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Molecular Mechanisms of Thyroid Hormone Synthesis and Secretion

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Book cover Principles of Endocrinology and Hormone Action

Part of the book series: Endocrinology ((ENDOCR))

Abstract

Thyroxine (T4) and triiodothyronine (T3), collectively called as thyroid hormones, are synthesized in the thyroid gland. Another molecule called reverse T3 (rT3), whose function is unknown, is also secreted from the thyroid gland. T4 is the major molecule synthesized and secreted from the thyroid gland, whereas other molecules are mainly generated in extrathyroidal tissues by deiodination of T4. The thyroid hormone synthetic pathway comprises the following steps: (1) thyroglobulin synthesis and secretion into the follicular lumen; (2) iodine uptake into the follicular epithelial cells; (3) iodine transport and efflux into the follicular lumen; (4) oxidation of iodine, iodination of thyroglobulin tyrosine residues, and coupling of iodotyrosines; (5) endocytosis of the thyroglobulin-thyroid hormone complex into follicular epithelial cells; (6) hydrolysis of the complex; and (7) secretion of thyroid hormone. Thyroid-stimulating hormone (thyrotropin) stimulates thyroid hormone synthesis. In this chapter, the outline of the thyroid hormone synthetic pathway is discussed. The mechanisms regulating thyroid hormone synthesis is briefly described. Furthermore, the clinical aspects of altered thyroid hormone synthesis and secretion induced by immunological or genetic abnormalities are also discussed.

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References

  • Amano I, Takatsuru Y, Toya S, Haijima A, Iwasaki T, Grasberger H, Refetoff S, Koibuchi N. Aberrant cerebellar development in mice lacking dual oxidase maturation factors. Thyroid. 2016;26:741ā€“52.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  • Bizhanova A, Kopp P. Controversies concerning the role of pendrin as an apical iodide transporter in thyroid follicular cells. Cell Physiol Biochem. 2011;28:485ā€“90.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • de Benoist B, McLean E, Andersson M, Rogers L. Iodine deficiency in 2007: global progress since 2003. Food Nutr Bull. 2008;29:195ā€“202.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  • Di Cosmo C, Liao X-H, Dumitrescu AM, Philp NJ, Weiss RE, Refetoff S. Mice deficient in MCT8 reveal a mechanism regulating thyroid hormone secretion. J Clin Invest. 2010;120:3377ā€“88.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  • FernĆ”ndez LP, LĆ³pez-MĆ”rquez A, Santisteban P. Thyroid transcription factors in development, differentiation and disease. Nat Rev Endocrinol. 2015;11:29ā€“42.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  • Grasberger H. Defects of thyroidal hydrogen peroxidase generation in congenital hypothyroidism. Mol Cell Endocrinol. 2010;322:99ā€“106.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87:489ā€“99.

    Google ScholarĀ 

  • Kasagi K, Takahashi N, Inoue G, Honda T, Kawachi Y, Izumi Y. Thyroid function in Japanese adults as assessed by a general health checkup system in relation with thyroid-related antibodies and other clinical parameters. Thyroid 2009;19:937ā€“44.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Kleinau G, Neumann S, GrĆ¼ters A, Krude H, Biebermann H. Novel insights on thyroid-stimulating hormone receptor signal transduction. Endocr Rev. 2013;34:691ā€“724.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  • Koibuchi N, Chin WW. Thyroid hormone action and brain development. Trends Endocrinol Metab. 2000;11:123ā€“8.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Kopp P, Pesce L, Solis JC. Pendred syndrome and iodide transport in the thyroid. Trend Endocrinol Metab. 2008;19:260ā€“8.

    ArticleĀ  CASĀ  Google ScholarĀ 

  • McLeod DSA, Cooper DS. The incidence and prevalence of thyroid autoimmunity. Endocrine. 2012;42:252ā€“65.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Park SM, Chatterjee VK. Genetics of congenital hypothyroidism. J Med Genet. 2005;42:379ā€“89.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  • Portulano C, Paroder-Belenitsky M, Carrasco N. The Na+/I- symporter (NIS): mechanism and medical impact. Endocr Rev. 2014;35:106ā€“49.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Rapoport B, McLachlan SM. TSH receptor cleavage into subunits and shedding of the a-subunit. Endocr Rev. 2016;37:114ā€“34.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  • Ruf J, Carayon P. Structural and functional aspects of thyroid peroxidase. Arch Biochem Biophys. 2006;445:269ā€“77.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Shimokawa N, Yousefi B, Morioka S, Yamaguchi S, Ohsawa A, Hayashi H, et al. Altered cerebellum development and dopamine distribution in a rat genetic model with congenital hypothyroidism. J Neuroendocrinol. 2014;26:164ā€“75.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Targovnik HM, Esperante SA, Rivolta CM. Genetics and phenomics of hypothyroidism and goiter due to thyroglobulin mutations. Mol Cell Endocrinol. 2010;322:44ā€“55.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  • Zimmermann MB. Iodine deficiency and endemic cretinism. In: Braverman LE, Cooper D, editors. The thyroid. A fundamental and clinical text. Philadelphia: Lippincott; 2013. p. 217ā€“41.

    Google ScholarĀ 

Further Reading

  • Koibuchi N, Yen PM, editors. Thyroid hormone disruption and neurodevelopment contemporary clinical neuroscience series. New York: Springer-Verlag; 2016. ISBN 978-1-4939-3737-0.

    Google ScholarĀ 

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Correspondence to Noriyuki Koibuchi .

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Koibuchi, N. (2018). Molecular Mechanisms of Thyroid Hormone Synthesis and Secretion. In: Belfiore, A., LeRoith, D. (eds) Principles of Endocrinology and Hormone Action. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-44675-2_5

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  • DOI: https://doi.org/10.1007/978-3-319-44675-2_5

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-44674-5

  • Online ISBN: 978-3-319-44675-2

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