Thyroid hormone actions

Fig. 2. Early events in thyroid-hormone action. Interaction of T with cell nuclear receptors (6).

Hormonal actions occur during sensitive periods in development, in adult life during natural endocrine cycles and in response to experience as well as during the aging process (see Ch. 30). As a result of their fundamental actions on cellular processes and genomic activity and of the control of their secretion by environmental signals, steroid and thyroid hormone actions on the brain provide unique insights into the plasticity of the brain and behavior (see also Ch. 50). 

Konig, S., Moura Neto, V. Thyroid hormone actions on neural cells. Cell. Mol. Neurobiol. 22 527-544, 2002. 

The three deiodinases have differing tissue distributions, substrate preferences, and values. This arrangement allows for control of thyroid hormone action at the cellular level. The source and quantity of Tj... 

E. N. Cheung (1995). Thyroid hormone action determination of hormone-receptor interaction using structural analogs and molecular modeling. Trends Pharmacol. Sci. 6 31-34. 

A model of thyroid hormone action is depicted in Figure 38-4, which shows the free forms of thyroid hormones, T4 and T3, dissociated from thyroid-binding proteins, entering the cell by active transport. Within the cell, T4 is converted to T3 by 5 -deiodinase, and the T3 enters the nucleus, where T3 binds to a specific T3 receptor protein, a member of the c-erb oncogene family. (This family also includes the steroid hormone receptors and receptors for vitamins A and D.) The T3 receptor exists in two forms, a and B. Differing concentrations of receptor forms in different tissues may account for variations in T3 effect on different tissues. 

Oetting A, Yen PM New insights into thyroid hormone action. Best Pract Res Clin Endocrinol Metab 2007 21 193. [PMID 17574003]... 

Zoeller RT, Crofton RM. 2000. Thyroid hormone action in fetal brain development and potential for distribution by environmental chemicals. Neurotoxicology 21(6) 935-946. 

Harvey CB, Williams GR. Mechanism of thyroid hormone action. Thyroid. 2002 12 441-446. 

Selenium Defense against oxidative stress regulates thyroid hormone action and metabolism of vitamin C and other molecules Men women 55 pg/d... 

A recently identified thyroid hormone cell surface receptor on the extracellular domain of integrin alphaVbeta (3) leads to the activation of the mitogen-activated protein kinase (MAPK) signal transduction cascade in human cell lines, Examples of MAPK-dependent thyroid hormone actions are plasma membrane ion pump stimulation and specific nuclear events, These events include serine phosphorylation of the nuclear thyroid hormone receptor, leading to co-activator protein recruitment and complex tissue responses, such as thyroid hormone-induced angiogenesis, The existence of this cell surface receptor means that the activity of the administered hormone could be limited through structural modification of the molecule to reproduce only those hormone actions initiated at the cell surface (8,9). 

Several important features of thyroid hormone action have been obtained by using pituitary cell lines (GH3, GH , GC) derived from the somatotrophs, i.e., the cells which synthesize and secrete growth hormone [43,46], When cultured in thyroid hormone depleted media such cells are responsive to thyroid hormone. Tsai and Samuels [47] first demonstrated that GH cells synthesize 3-10-times more GH when cultured in the presence of physiological concentration of T3 (0.1-1 nM). A detectable increase in GH synthesis occurs 45-60 min after significant binding to nuclear sites. Such an increase is paralleled by changes in total cytoplasmic GH mRNA... 

Thyroid hormone activity is determined predominantly by intracellular concentrations of (free) T3 in the tissues. This T3 bioavailability depends on 1) the secretion of T4 and T3 by the thyroid, 2) the conversion of T4 to T3 outside the thyroid, 3) the metabolic clearance of T3 and 4) exchange of T4 and T3 between plasma and tissues. It is the purpose of this chapter to review recent advancements in the study of the transport and metabolism of thyroid hormone. Especially the role of deiodination, conjugation and tissue uptake mechanisms will be emphasized in the regulation of thyroid hormone action. 

Oppenheimer, J.H. and Samuels. H.H. eds. (1983) Molecular Basis of Thyroid Hormone Action. Academic Press, New York. 

Oppenheimer JH, Schwartz HL, Surks Ml, Koerner D, Dillmann WH. Nuclear receptors and the initiation of thyroid hormone action. Recent Prog. Horm. Res. 1976 32 529-565. 

Quick relief can be obtained with a p-adrenoceptor blocking drug (judge dose by heart rate) though these do not block all the metabolic effects of the hormone, e.g. on the myocardium, and the basal metabolic rate is unchanged. For this reason they should not be used as sole therapy except in mild thyrotoxicosis in preparation for radioiodine treatment, and should be continued in these patients until the radioiodine has taken effect. They do not alter the course of the disease, nor biochemical tests of thyroid function. Any effect on thyroid hormonal action on peripheral tissues is clinically unimportant. It is desirable to choose a drug that is nonselective for pj and p2 receptors and lacks partial agonist effect (e.g. propranolol 20-80 mg 6-8-hourly, or timolol 5 mg once daily). Usual contraindications to P-blockade (see p. 478) should be observed, especially asthma. 

MuiJer, M, J Acheson, K, J Jequter, E., and Burger, A. G. (1990). Thyroid hormone action on Lpid metabolism in humans A role for endogenous insulin. Metabolism 39,480-485. Ohtaki, S., Nekagpwa, H-, Nakamura, S Nakamura, M-, and Vamazaki, J. (1985). Characterization of hog thyroid peroxidase- /. fSiof. CfwFri- 260,441-448. 

Brent GA. The molecular basis of thyroid hormone action. N Engl J Med 1994 331 847-53. 

Lim, W., N.-H. Nguyen, H.Y. Yang, T.S. Scanlan and J.D. Furlow. A thyroid hormone antagonist that inhibits thyroid hormone action in vivo. J. Biol. Chem. 277 35664-35670, 2002. 

Motomura K, Brent GA. Mechanisms of thyroid hormone action. Implications for the clinical manifestation of thyrotoxicosis. Endocrinol Metab Clin North Am 1998 27 1-23. 

Brent GA. Thyroid hormone action Down novel paths. Focus on thyroid hormone induces activation of mitogen-activated protein kinase in cultured cells. Am J Physiol 1999 276 C1012-C1013. 

Normal proliferation of somatic cells requires both thyroid hormone and growth hormone. Thyroid hormone stimulates growth hormone secretion, and many thyroid hormone actions on the insulin-Uke growth factor (IGF) system can be explained by this mechanism. 

Zoeller, RT University of Massachusetts PCB and thyroid hormone action in developing cochlea NIEHS... 

Kohele j (1996) Thyroid hormone deiodinases — a selenoenzyme family action as gate keepers to thyroid hormone action. Acta Med Austr 23 17-30. 

Zoeller, R.T. (2001). Polychlorinated biphenyls as disrupters of thyroid hormone action. In (eds L.W. Robertson and L.G. Hansen), PCBs, Recent Advances in Environmental Toxicology and Health Effects. The University Press of Kentucky, Kentucky, pp. 265—269. 

Figure 38.2 Possible sites of inhibitory actions of soy isoflavones on iodine utilization and thyroid hormone biosynthesis and actions. Soy isoflavonoids, genistein and daidzein, inhibit oxidation of iodide by thyroid peroxidase at the apical membrane of thyroid follicular cells, followed by iodination of tyrosine residues in thyroglobulin and their coupling in colloid. In addition, they may affect deiodination of iodothyronines and interfere with thyroid hormone binding to transthyretin. Full arrows indicate the sites of inhibition. So far, only few reports concern the effect of thyroid hormone actions in target cells.

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