Skip to main content
SpringerLink
Log in

The Thyroid Hormone Axis: Its Roles in Body Weight Regulation, Obesity, and Weight Loss

  • Chapter
  • First Online:
Book cover Textbook of Energy Balance, Neuropeptide Hormones, and Neuroendocrine Function

  • 814 Accesses

Abstract

In humans and other vertebrates, thyroid hormone is essential to the development and function of every tissue in the body. During adulthood, thyroid hormone is critical to mediating changes in metabolism as it is key to the regulation of resting energy expenditure, body temperature, and hepatic lipid metabolism, to name a few. The hypothalamic-pituitary-thyroid (HPT) axis functions as a negative feedback loop where thyrotropin-releasing hormone (TRH) is released from neurons in the paraventricular nucleus of the hypothalamus and stimulates the secretion of thyroid-stimulating hormone (TSH) from the pituitary. TSH signals the release of thyroid hormones, both the prohormone thyroxine (T4) and the active hormone triiodothyronine (T3) from the thyroid. Through central actions, TRH and TSH are negatively regulated by T3 at several levels including gene transcription and prohormone processing. The HPT axis is a dynamic system that responds to environment including food availability, environmental temperature, weight loss, and illness normally through central mechanisms. The following chapter will focus on the regulation of thyroid hormone, its role in body weight, and how weight loss can affect thyroid hormone levels. Currently, thyroid hormone is a poor therapeutic to treat obesity and to elevate energy expenditure because it has detrimental effects such as atrial fibrillation, osteoporosis, and muscle wasting. Researchers are focusing on thyroid hormone analogs as therapeutics for weight loss to eliminate the negative side effects. As detailed below, thyroid hormone action in peripheral tissues can be just as important to energy expenditure as the central regulation of thyroid hormone.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abel, E. D., Ahima, R. S., Boers, M. E., Elmquist, J. K., & Wondisford, F. E. (2001). Critical role for thyroid hormone receptor beta2 in the regulation of paraventricular thyrotropin-releasing hormone neurons. The Journal of Clinical Investigation, 107, 1017–1023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ahima, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., & Flier, J. S. (1996). Role of leptin in the neuroendocrine response to fasting. Nature, 382, 250–252.

    Article  CAS  PubMed  Google Scholar 

  • Alland, L., Muhle, R., Hou, H., Jr., Potes, J., Chin, L., Schreiber-Agus, N., & DePinho, R. A. (1997). Role for N-CoR and histone deacetylase in Sin3-mediated transcriptional repression. Nature, 387, 49–55.

    Article  CAS  PubMed  Google Scholar 

  • Antonelli, A., Fallahi, P., Ferrari, S. M., Di Domenicantonio, A., Moreno, M., Lanni, A., & Goglia, F. (2011). 3,5-diiodo-L-thyronine increases resting metabolic rate and reduces body weight without undesirable side effects. Journal of Biological Regulators and Homeostatic Agents, 25, 655–660.

    PubMed  CAS  Google Scholar 

  • Astapova, I., Lee, L. J., Morales, C., Tauber, S., Bilban, M., & Hollenberg, A. N. (2008). The nuclear corepressor, NCoR, regulates thyroid hormone action in vivo. Proceedings of the National Academy of Sciences of the United States of America, 105, 19544–19549.

    Article  PubMed  PubMed Central  Google Scholar 

  • Astapova, I., et al. (2011). The nuclear receptor corepressor (NCoR) controls thyroid hormone sensitivity and the set point of the hypothalamic-pituitary-thyroid axis. Molecular Endocrinology (Baltimore, MD), 25, 212–224.

    Article  CAS  Google Scholar 

  • Barker, S. B. (1951). Mechanism of action of the thyroid hormone. Physiological Reviews, 31, 205–243.

    Article  CAS  PubMed  Google Scholar 

  • Baxter, J. D., & Webb, P. (2009). Thyroid hormone mimetics: Potential applications in atherosclerosis, obesity and type 2 diabetes. Nature Reviews. Drug Discovery, 8, 308–320. https://doi.org/10.1038/nrd2830.

    Article  PubMed  CAS  Google Scholar 

  • Beck-Peccoz, P., Amr, S., Menezes-Ferreira, M. M., Faglia, G., & Weintraub, B. D. (1985). Decreased receptor binding of biologically inactive thyrotropin in central hypothyroidism. Effect of treatment with thyrotropin-releasing hormone. The New England Journal of Medicine, 312, 1085–1090. https://doi.org/10.1056/NEJM198504253121703.

    Article  PubMed  CAS  Google Scholar 

  • Benvenga, S., Cahnmann, H. J., Rader, D., Kindt, M., Facchiano, A., & Robbins, J. (1994). Thyroid hormone binding to isolated human apolipoproteins A-II, C-I, C-II, and C-III: Homology in thyroxine binding sites. Thyroid, 4, 261–267. https://doi.org/10.1089/thy.1994.4.261.

    Article  PubMed  CAS  Google Scholar 

  • Bjorbaek, C., & Hollenberg, A. N. (2002). Leptin and melanocortin signaling in the hypothalamus. Vitamins and Hormones, 65, 281–311.

    Article  CAS  PubMed  Google Scholar 

  • Blake, N. G., Eckland, D. J., Foster, O. J., & Lightman, S. L. (1991). Inhibition of hypothalamic thyrotropin-releasing hormone messenger ribonucleic acid during food deprivation. Endocrinology, 129, 2714–2718.

    Article  CAS  PubMed  Google Scholar 

  • Blake, N. G., Johnson, M. R., Eckland, D. J., Foster, O. J., & Lightman, S. L. (1992). Effect of food deprivation and altered thyroid status on the hypothalamic-pituitary-thyroid axis in the rat. The Journal of Endocrinology, 133, 183–188.

    Article  CAS  PubMed  Google Scholar 

  • Bobek, S., Sechman, A., Niezgoda, J., & Jacek, T. (2002). Reverse 3,3′,5′-triiodothyronine suppresses increase in free fatty acids in chickens elicited by dexamethasone or adrenaline. Journal of Veterinary Medicine. A, Physiology, Pathology, Clinical Medicine, 49, 121–124.

    Article  CAS  PubMed  Google Scholar 

  • Bochukova, E., et al. (2012). A mutation in the thyroid hormone receptor alpha gene. The New England Journal of Medicine, 366, 243–249. https://doi.org/10.1056/NEJMoa1110296.

    Article  PubMed  CAS  Google Scholar 

  • Bowers, C. R., Redding, T. W., & Schally, A. V. (1965). Effect of thyrotropin releasing factor (TRF) of ovine, bovine, porcine and human origin on thyrotropin release in vitro and in vivo. Endocrinology, 77, 609–616. https://doi.org/10.1210/endo-77-4-609.

    Article  PubMed  CAS  Google Scholar 

  • Brent, G. A. (2012). Mechanisms of thyroid hormone action. The Journal of Clinical Investigation, 122, 3035–3043. https://doi.org/10.1172/JCI60047.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Burch, H. B., & Wartofsky, L. (1993). Life-threatening thyrotoxicosis. Thyroid storm Endocrinol Metab Clin North Am, 22, 263–277.

    Article  PubMed  CAS  Google Scholar 

  • Cable, E. E., et al. (2009). Reduction of hepatic steatosis in rats and mice after treatment with a liver-targeted thyroid hormone receptor agonist. Hepatology, 49, 407–417. https://doi.org/10.1002/hep.22572.

    Article  PubMed  CAS  Google Scholar 

  • Celi, F. S., et al. (2011). Metabolic effects of liothyronine therapy in hypothyroidism: A randomized, double-blind, crossover trial of liothyronine versus levothyroxine. The Journal of Clinical Endocrinology and Metabolism, 96, 3466–3474. https://doi.org/10.1210/jc.2011-1329.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chiamolera, M. I., & Wondisford, F. E. (2009). Minireview: Thyrotropin-releasing hormone and the thyroid hormone feedback mechanism. Endocrinology, 150, 1091–1096.

    Article  CAS  PubMed  Google Scholar 

  • Connors, J. M., DeVito, W. J., & Hedge, G. A. (1985). Effects of food deprivation on the feedback regulation of the hypothalamic-pituitary-thyroid axis of the rat. Endocrinology, 117, 900–906.

    Article  CAS  PubMed  Google Scholar 

  • Costa-e-Sousa, R. H., & Hollenberg, A. N. (2012). Minireview: The neural regulation of the hypothalamic-pituitary-thyroid axis. Endocrinology, 153, 4128–4135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cypess, A. M., et al. (2009). Identification and importance of brown adipose tissue in adult humans. The New England Journal of Medicine, 360, 1509–1517. https://doi.org/10.1056/NEJMoa0810780.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Du Bois, E. F. (1936). Basal metabolism in health and disease (3rd ed.). Philadelphia: Lea & Febiger.

    Google Scholar 

  • Erion, M. D., et al. (2007). Targeting thyroid hormone receptor-beta agonists to the liver reduces cholesterol and triglycerides and improves the therapeutic index. Proceedings of the National Academy of Sciences of the United States of America, 104, 15490–15495. https://doi.org/10.1073/pnas.0702759104.

    Article  PubMed  PubMed Central  Google Scholar 

  • Farwell, A. P., Lynch, R. M., Okulicz, W. C., Comi, A. M., & Leonard, J. L. (1990). The actin cytoskeleton mediates the hormonally regulated translocation of type II iodothyronine 5′-deiodinase in astrocytes. The Journal of Biological Chemistry, 265, 18546–18553.

    PubMed  CAS  Google Scholar 

  • Fekete, C., et al. (2001). Neuropeptide Y has a central inhibitory action on the hypothalamic-pituitary-thyroid axis. Endocrinology, 142, 2606–2613.

    Article  CAS  PubMed  Google Scholar 

  • Fekete, C., et al. (2000). alpha-Melanocyte-stimulating hormone is contained in nerve terminals innervating thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus and prevents fasting-induced suppression of prothyrotropin-releasing hormone gene expression. The Journal of Neuroscience, 20, 1550–1558.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fekete, C., Sarkar, S., Rand, W. M., Harney, J. W., Emerson, C. H., Bianco, A. C., & Lechan, R. M. (2002). Agouti-related protein (AGRP) has a central inhibitory action on the hypothalamic-pituitary-thyroid (HPT) axis; comparisons between the effect of AGRP and neuropeptide Y on energy homeostasis and the HPT axis. Endocrinology, 143, 3846–3853.

    Article  CAS  PubMed  Google Scholar 

  • Flores-Morales, A., Gullberg, H., Fernandez, L., Stahlberg, N., Lee, N. H., Vennstrom, B., & Norstedt, G. (2002). Patterns of liver gene expression governed by TRbeta. Molecular Endocrinology (Baltimore, MD), 16, 1257–1268. https://doi.org/10.1210/mend.16.6.0846.

    Article  CAS  Google Scholar 

  • Forrest, D., Erway, L. C., Ng, L., Altschuler, R., & Curran, T. (1996). Thyroid hormone receptor beta is essential for development of auditory function. Nature Genetics, 13, 354–357. https://doi.org/10.1038/ng0796-354.

    Article  PubMed  CAS  Google Scholar 

  • Forrest, D., & Vennstrom, B. (2000). Functions of thyroid hormone receptors in mice. Thyroid, 10, 41–52. https://doi.org/10.1089/thy.2000.10.41.

    Article  PubMed  CAS  Google Scholar 

  • Friesema, E. C., Jansen, J., & Visser, T. J. (2005). Thyroid hormone transporters. Biochemical Society Transactions, 33, 228–232. https://doi.org/10.1042/BST0330228.

    Article  PubMed  CAS  Google Scholar 

  • Friesema, E. C., Visser, W. E., & Visser, T. J. (2010). Genetics and phenomics of thyroid hormone transport by MCT8. Molecular and Cellular Endocrinology, 322, 107–113. https://doi.org/10.1016/j.mce.2010.01.016.

    Article  PubMed  CAS  Google Scholar 

  • Geras, E. J., & Gershengorn, M. C. (1982). Evidence that TRH stimulates secretion of TSH by two calcium-mediated mechanisms. The American Journal of Physiology, 242, E109–E114.

    Article  CAS  PubMed  Google Scholar 

  • Gereben, B., McAninch, E. A., Ribeiro, M. O., & Bianco, A. C. (2015). Scope and limitations of iodothyronine deiodinases in hypothyroidism. Nature Reviews. Endocrinology, 11, 642–652. https://doi.org/10.1038/nrendo.2015.155.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Giudetti, A. M., Leo, M., Siculella, L., & Gnoni, G. V. (2006). Hypothyroidism down-regulates mitochondrial citrate carrier activity and expression in rat liver. Biochimica et Biophysica Acta, 1761, 484–491. https://doi.org/10.1016/j.bbalip.2006.03.021.

    Article  PubMed  CAS  Google Scholar 

  • Goldstein, J. L., DeBose-Boyd, R. A., & Brown, M. S. (2006). Protein sensors for membrane sterols. Cell, 124, 35–46. https://doi.org/10.1016/j.cell.2005.12.022.

    Article  PubMed  CAS  Google Scholar 

  • Grant, N. (2007). The role of triiodothyronine-induced substrate cycles in the hepatic response to overnutrition: Thyroid hormone as an antioxidant. Medical Hypotheses, 68, 641–649. https://doi.org/10.1016/j.mehy.2006.07.045.

    Article  PubMed  CAS  Google Scholar 

  • Grasselli, E., Canesi, L., Voci, A., De Matteis, R., Demori, I., Fugassa, E., & Vergani, L. (2008). Effects of 3,5-diiodo-L-thyronine administration on the liver of high fat diet-fed rats. Experimental Biology and Medicine (Maywood, N.J.), 233, 549–557. https://doi.org/10.3181/0710-RM-266.

    Article  CAS  Google Scholar 

  • Greer, M. A. (1951). Evidence of hypothalamic control of the pituitary release of thyrotropin. Proceedings of the Society for Experimental Biology and Medicine, 77, 603–608.

    Article  CAS  PubMed  Google Scholar 

  • Guillemin, R., Sakiz, E., & Ward, D. N. (1965). Further purification of Tsh-releasing factor (Trf) from sheep hypothalamic tissues, with observations on the amino acid composition. Proceedings of the Society for Experimental Biology and Medicine, 118, 1132–1137.

    Article  CAS  PubMed  Google Scholar 

  • Guillemin, R., Yamazaki, E., Gard, D. A., Jutisz, M., & Sakiz, E. (1963). In vitro secretion of thyrotropin (Tsh): Stimulation by a hypothalamic peptide (Trf). Endocrinology, 73, 564–572. https://doi.org/10.1210/endo-73-5-564.

    Article  PubMed  CAS  Google Scholar 

  • Gullberg, H., Rudling, M., Forrest, D., Angelin, B., & Vennstrom, B. (2000). Thyroid hormone receptor beta-deficient mice show complete loss of the normal cholesterol 7alpha-hydroxylase (CYP7A) response to thyroid hormone but display enhanced resistance to dietary cholesterol. Molecular Endocrinology (Baltimore, MD), 14, 1739–1749. https://doi.org/10.1210/mend.14.11.0548.

    Article  CAS  Google Scholar 

  • Gullberg, H., Rudling, M., Salto, C., Forrest, D., Angelin, B., & Vennstrom, B. (2002). Requirement for thyroid hormone receptor beta in T3 regulation of cholesterol metabolism in mice. Molecular Endocrinology (Baltimore, MD), 16, 1767–1777. https://doi.org/10.1210/me.2002-0009.

    Article  CAS  Google Scholar 

  • Haber, R. S., Ismail-Beigi, F., & Loeb, J. N. (1988). Time course of na,k transport and other metabolic responses to thyroid hormone in clone 9 cells. Endocrinology, 123, 238–247. https://doi.org/10.1210/endo-123-1-238.

    Article  PubMed  CAS  Google Scholar 

  • Halachmi, S., Marden, E., Martin, G., MacKay, H., Abbondanza, C., & Brown, M. (1994). Estrogen receptor-associated proteins: Possible mediators of hormone-induced transcription. Science (New York, NY), 264, 1455–1458.

    Article  CAS  Google Scholar 

  • Heijlen, M., et al. (2014). Knockdown of type 3 iodothyronine deiodinase severely perturbs both embryonic and early larval development in zebrafish. Endocrinology, 155, 1547–1559. https://doi.org/10.1210/en.2013-1660.

    Article  PubMed  CAS  Google Scholar 

  • Heinzel, T., et al. (1997). A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature, 387, 43–48.

    Article  CAS  PubMed  Google Scholar 

  • Hu, X., & Lazar, M. A. (1999). The CoRNR motif controls the recruitment of corepressors by nuclear hormone receptors. Nature, 402, 93–96. https://doi.org/10.1038/47069.

    Article  PubMed  CAS  Google Scholar 

  • Jackson-Hayes, L., et al. (2003). A thyroid hormone response unit formed between the promoter and first intron of the carnitine palmitoyltransferase-Ialpha gene mediates the liver-specific induction by thyroid hormone. The Journal of Biological Chemistry, 278, 7964–7972. https://doi.org/10.1074/jbc.M211062200.

    Article  PubMed  CAS  Google Scholar 

  • Jepsen, K., Gleiberman, A. S., Shi, C., Simon, D. I., & Rosenfeld, M. G. (2008). Cooperative regulation in development by SMRT and FOXP1. Genes & Development, 22, 740–745. https://doi.org/10.1101/gad.1637108.

    Article  CAS  Google Scholar 

  • Jepsen, K., et al. (2000). Combinatorial roles of the nuclear receptor corepressor in transcription and development. Cell, 102, 753–763.

    Article  CAS  PubMed  Google Scholar 

  • Kaneshige, M., et al. (2001). A targeted dominant negative mutation of the thyroid hormone alpha 1 receptor causes increased mortality, infertility, and dwarfism in mice. Proceedings of the National Academy of Sciences of the United States of America, 98, 15095–15100. https://doi.org/10.1073/pnas.261565798.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Katzeff, H. L., Yang, M. U., Presta, E., Leibel, R. L., Hirsch, J., & Van Itallie, T. B. (1990). Calorie restriction and iopanoic acid effects on thyroid hormone metabolism. The American Journal of Clinical Nutrition, 52, 263–266.

    Article  CAS  PubMed  Google Scholar 

  • Klein, I., & Danzi, S. (2007). Thyroid disease and the heart. Circulation, 116, 1725–1735. https://doi.org/10.1161/CIRCULATIONAHA.106.678326.

    Article  PubMed  Google Scholar 

  • Klieverik, L. P., et al. (2009). Thyroid hormone modulates glucose production via a sympathetic pathway from the hypothalamic paraventricular nucleus to the liver. Proceedings of the National Academy of Sciences of the United States of America, 106, 5966–5971. https://doi.org/10.1073/pnas.0805355106.

    Article  PubMed  PubMed Central  Google Scholar 

  • Klieverik, L. P., Sauerwein, H. P., Ackermans, M. T., Boelen, A., Kalsbeek, A., & Fliers, E. (2008). Effects of thyrotoxicosis and selective hepatic autonomic denervation on hepatic glucose metabolism in rats. American Journal of Physiology, 294, E513–E520. https://doi.org/10.1152/ajpendo.00659.2007.

    Article  PubMed  CAS  Google Scholar 

  • Kopp, P. (2005). Thyroid hormone synthesis: Thyroid iodine metabolism. In L. U. R. Braverman (Ed.), Wegner and Ingbar's the thyroid: A fundamental and clinical text (pp. 52–76). USA: Lippincott Williams & Wilkins.

    Google Scholar 

  • Lanni, A., et al. (2005). 3,5-diiodo-L-thyronine powerfully reduces adiposity in rats by increasing the burning of fats. The FASEB Journal, 19, 1552–1554. https://doi.org/10.1096/fj.05-3977fje.

    Article  PubMed  CAS  Google Scholar 

  • Lazar, M. A. (1993). Thyroid hormone receptors: Multiple forms, multiple possibilities. Endocrine Reviews, 14, 184–193.

    PubMed  CAS  Google Scholar 

  • Le, T. N., Celi, F. S., & Wickham, E. P., 3rd. (2016). Thyrotropin levels are associated with cardiometabolic risk factors in euthyroid adolescents. Thyroid, 26, 1441–1449. https://doi.org/10.1089/thy.2016.0055.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lechan, R. M., & Hollenberg, A. N. (2003). Thyrotropin-releasing hormone (TRH). In H. L. Henry & A. W. Norman (Eds.), Encyclopedia of hormones (pp. 510–524). New York: Elsevier Science.

    Chapter  Google Scholar 

  • Lechan, R. M., Wu, P., Jackson, I. M., Wolf, H., Cooperman, S., Mandel, G., & Goodman, R. H. (1986). Thyrotropin-releasing hormone precursor: Characterization in rat brain. Science (New York, NY), 231, 159–161.

    Article  CAS  Google Scholar 

  • Legradi, G., Emerson, C. H., Ahima, R. S., Flier, J. S., & Lechan, R. M. (1997). Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus. Endocrinology, 138, 2569–2576.

    Article  CAS  PubMed  Google Scholar 

  • Legradi, G., & Lechan, R. M. (1998). The arcuate nucleus is the major source for neuropeptide Y-innervation of thyrotropin-releasing hormone neurons in the hypothalamic paraventricular nucleus. Endocrinology, 139, 3262–3270.

    Article  CAS  PubMed  Google Scholar 

  • Lombardi, A., Lanni, A., Moreno, M., Brand, M. D., & Goglia, F. (1998). Effect of 3,5-di-iodo-L-thyronine on the mitochondrial energy-transduction apparatus. The Biochemical Journal, 330(Pt 1), 521–526.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lonard, D. M., & O'Malley, B. W. (2007). Nuclear receptor coregulators: Judges, juries, and executioners of cellular regulation. Molecular Cell, 27, 691–700. https://doi.org/10.1016/j.molcel.2007.08.012.

    Article  PubMed  CAS  Google Scholar 

  • Lopez, D., Abisambra Socarras, J. F., Bedi, M., & Ness, G. C. (2007). Activation of the hepatic LDL receptor promoter by thyroid hormone. Biochimica et Biophysica Acta, 1771, 1216–1225. https://doi.org/10.1016/j.bbalip.2007.05.001.

    Article  PubMed  CAS  Google Scholar 

  • Maglich, J. M., Watson, J., McMillen, P. J., Goodwin, B., Willson, T. M., & Moore, J. T. (2004). The nuclear receptor CAR is a regulator of thyroid hormone metabolism during caloric restriction. The Journal of Biological Chemistry, 279, 19832–19838.

    Article  CAS  PubMed  Google Scholar 

  • Mangus-Levy, A. (1895). Uber den respiratorischen Gaswechsel unter dem Einfluss der Thyroiden sowie unter verschiedenen physiologischen. Zustanden Berlin klinische Wochenschrift, 32, 650–652.

    Google Scholar 

  • Martin, J. B., Boshans, R., & Reichlin, S. (1970). Feedback regulation of TSH secretion in rats with hypothalamic lesions. Endocrinology, 87, 1032–1040. https://doi.org/10.1210/endo-87-5-1032.

    Article  PubMed  CAS  Google Scholar 

  • Menezes-Ferreira, M. M., Petrick, P. A., & Weintraub, B. D. (1986). Regulation of thyrotropin (TSH) bioactivity by TSH-releasing hormone and thyroid hormone. Endocrinology, 118, 2125–2130. https://doi.org/10.1210/endo-118-5-2125.

    Article  PubMed  CAS  Google Scholar 

  • Mittag, J., et al. (2013). Thyroid hormone is required for hypothalamic neurons regulating cardiovascular functions. The Journal of Clinical Investigation, 123, 509–516. https://doi.org/10.1172/JCI65252.

    Article  PubMed  CAS  Google Scholar 

  • Mol, J. A., & Visser, T. J. (1985). Rapid and selective inner ring deiodination of thyroxine sulfate by rat liver deiodinase. Endocrinology, 117, 8–12.

    Article  CAS  PubMed  Google Scholar 

  • Mollica, M. P., et al. (2009). 3,5-diiodo-l-thyronine, by modulating mitochondrial functions, reverses hepatic fat accumulation in rats fed a high-fat diet. Journal of Hepatology, 51, 363–370. https://doi.org/10.1016/j.jhep.2009.03.023.

    Article  PubMed  CAS  Google Scholar 

  • Moreno, M., Lanni, A., Lombardi, A., & Goglia, F. (1997). How the thyroid controls metabolism in the rat: Different roles for triiodothyronine and diiodothyronines. The Journal of Physiology, 505(Pt 2), 529–538.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moreno, M., et al. (2011). 3,5-Diiodo-L-thyronine prevents high-fat-diet-induced insulin resistance in rat skeletal muscle through metabolic and structural adaptations. The FASEB Journal, 25, 3312–3324. https://doi.org/10.1096/fj.11-181982.

    Article  PubMed  CAS  Google Scholar 

  • Mullur, R., Liu, Y. Y., & Brent, G. A. (2014). Thyroid hormone regulation of metabolism. Physiological Reviews, 94, 355–382. https://doi.org/10.1152/physrev.00030.2013.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nagy, L., et al. (1997). Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. Cell, 89, 373–380.

    Article  CAS  PubMed  Google Scholar 

  • Nagy, L., et al. (1999). Mechanism of corepressor binding and release from nuclear hormone receptors. Genes & Development, 13, 3209–3216.

    Article  CAS  Google Scholar 

  • Ng, L., Cordas, E., Wu, X., Vella, K. R., Hollenberg, A. N., & Forrest, D. (2015). Age-related hearing loss and degeneration of Cochlear hair cells in mice lacking thyroid hormone receptor beta1. Endocrinology, 156, 3853–3865. https://doi.org/10.1210/en.2015-1468.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ng, L., et al. (2004). Hearing loss and retarded cochlear development in mice lacking type 2 iodothyronine deiodinase. Proceedings of the National Academy of Sciences of the United States of America, 101, 3474–3479. https://doi.org/10.1073/pnas.0307402101.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ng, L., et al. (2009). A protective role for type 3 deiodinase, a thyroid hormone-inactivating enzyme, in cochlear development and auditory function. Endocrinology, 150, 1952–1960. https://doi.org/10.1210/en.2008-1419.

    Article  PubMed  CAS  Google Scholar 

  • Ng, L., et al. (2001). A thyroid hormone receptor that is required for the development of green cone photoreceptors. Nature Genetics, 27, 94–98. https://doi.org/10.1038/83829.

    Article  PubMed  CAS  Google Scholar 

  • Nikrodhanond, A. A., et al. (2006). Dominant role of thyrotropin-releasing hormone in the hypothalamic-pituitary-thyroid axis. The Journal of Biological Chemistry, 281, 5000–5007.

    Article  CAS  PubMed  Google Scholar 

  • Onate, S. A., Tsai, S. Y., Tsai, M. J., & O'Malley, B. W. (1995). Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science (New York, NY), 270, 1354–1357.

    Article  CAS  Google Scholar 

  • Paradies, G., & Ruggiero, F. M. (1990). Enhanced activity of the tricarboxylate carrier and modification of lipids in hepatic mitochondria from hyperthyroid rats. Archives of Biochemistry and Biophysics, 278, 425–430.

    Article  CAS  PubMed  Google Scholar 

  • Paradies, G., Ruggiero, F. M., Petrosillo, G., & Quagliariello, E. (1996). Stimulation of carnitine acylcarnitine translocase activity in heart mitochondria from hyperthyroid rats. FEBS Letters, 397, 260–262.

    Article  CAS  PubMed  Google Scholar 

  • Paradies, G., Ruggiero, F. M., Petrosillo, G., & Quagliariello, E. (1997). Alterations in carnitine-acylcarnitine translocase activity and in phospholipid composition in heart mitochondria from hypothyroid rats. Biochimica et Biophysica Acta, 1362, 193–200.

    Article  CAS  PubMed  Google Scholar 

  • Park, E. A., Song, S., Vinson, C., & Roesler, W. J. (1999). Role of CCAAT enhancer-binding protein beta in the thyroid hormone and cAMP induction of phosphoenolpyruvate carboxykinase gene transcription. The Journal of Biological Chemistry, 274, 211–217.

    Article  CAS  PubMed  Google Scholar 

  • Perello, M., Friedman, T., Paez-Espinosa, V., Shen, X., Stuart, R. C., & Nillni, E. A. (2006). Thyroid hormones selectively regulate the posttranslational processing of prothyrotropin-releasing hormone in the paraventricular nucleus of the hypothalamus. Endocrinology, 147, 2705–2716.

    Article  CAS  PubMed  Google Scholar 

  • Perello, M., & Nillni, E. A. (2007). The biosynthesis and processing of neuropeptides: Lessons from prothyrotropin releasing hormone (proTRH). Frontiers in Bioscience, 12, 3554–3565.

    Article  CAS  PubMed  Google Scholar 

  • Perissi, V., et al. (1999). Molecular determinants of nuclear receptor-corepressor interaction. Genes & Development, 13, 3198–3208.

    Article  CAS  Google Scholar 

  • Perra, A., et al. (2008). Thyroid hormone (T3) and TRbeta agonist GC-1 inhibit/reverse nonalcoholic fatty liver in rats. The FASEB Journal, 22, 2981–2989. https://doi.org/10.1096/fj.08-108464.

    Article  PubMed  CAS  Google Scholar 

  • Piehl, S., Hoefig, C. S., Scanlan, T. S., & Kohrle, J. (2011). Thyronamines--past, present, and future. Endocrine Reviews, 32, 64–80. https://doi.org/10.1210/er.2009-0040.

    Article  PubMed  CAS  Google Scholar 

  • Psarra, A. M., Solakidi, S., & Sekeris, C. E. (2006). The mitochondrion as a primary site of action of steroid and thyroid hormones: Presence and action of steroid and thyroid hormone receptors in mitochondria of animal cells. Molecular and Cellular Endocrinology, 246, 21–33. https://doi.org/10.1016/j.mce.2005.11.025.

    Article  PubMed  CAS  Google Scholar 

  • Qatanani, M., Zhang, J., & Moore, D. D. (2005). Role of the constitutive androstane receptor in xenobiotic-induced thyroid hormone metabolism. Endocrinology, 146, 995–1002.

    Article  CAS  PubMed  Google Scholar 

  • Refetoff, S., Weiss, R. E., & Usala, S. J. (1993). The syndromes of resistance to thyroid hormone. Endocrine Reviews, 14, 348–399.

    PubMed  CAS  Google Scholar 

  • Rodgers, J. T., Lerin, C., Gerhart-Hines, Z., & Puigserver, P. (2008). Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways. FEBS Letters, 582, 46–53. https://doi.org/10.1016/j.febslet.2007.11.034.

    Article  PubMed  CAS  Google Scholar 

  • Rosenbaum, M., et al. (2005). Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. The Journal of Clinical Investigation, 115, 3579–3586.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosenbaum, M., Murphy, E. M., Heymsfield, S. B., Matthews, D. E., & Leibel, R. L. (2002). Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones. The Journal of Clinical Endocrinology and Metabolism, 87, 2391–2394.

    Article  CAS  PubMed  Google Scholar 

  • Santillo, A., Burrone, L., Falvo, S., Senese, R., Lanni, A., & Chieffi Baccari, G. (2013). Triiodothyronine induces lipid oxidation and mitochondrial biogenesis in rat Harderian gland. The Journal of Endocrinology, 219, 69–78. https://doi.org/10.1530/JOE-13-0127.

    Article  PubMed  CAS  Google Scholar 

  • Schally, A. V., Redding, T. W., Bowers, C. Y., & Barrett, J. F. (1969). Isolation and properties of porcine thyrotropin-releasing hormone. The Journal of Biological Chemistry, 244, 4077–4088.

    PubMed  CAS  Google Scholar 

  • Schaner, P., Todd, R. B., Seidah, N. G., & Nillni, E. A. (1997). Processing of prothyrotropin-releasing hormone by the family of prohormone convertases. The Journal of Biological Chemistry, 272, 19958–19968.

    Article  CAS  PubMed  Google Scholar 

  • Segerson, T. P., Kauer, J., Wolfe, H. C., Mobtaker, H., Wu, P., Jackson, I. M., & Lechan, R. M. (1987). Thyroid hormone regulates TRH biosynthesis in the paraventricular nucleus of the rat hypothalamus. Science (New York, NY), 238, 78–80.

    Article  CAS  Google Scholar 

  • Shin, D. J., & Osborne, T. F. (2003). Thyroid hormone regulation and cholesterol metabolism are connected through sterol regulatory element-binding Protein-2 (SREBP-2). The Journal of Biological Chemistry, 278, 34114–34118. https://doi.org/10.1074/jbc.M305417200.

    Article  PubMed  CAS  Google Scholar 

  • Shupnik, M. A., Weck, J., & Hinkle, P. M. (1996). Thyrotropin (TSH)-releasing hormone stimulates TSH beta promoter activity by two distinct mechanisms involving calcium influx through L type Ca2+ channels and protein kinase C. Molecular Endocrinology (Baltimore, MD), 10, 90–99. https://doi.org/10.1210/mend.10.1.8838148.

    Article  CAS  Google Scholar 

  • Siegrist-Kaiser, C. A., Juge-Aubry, C., Tranter, M. P., Ekenbarger, D. M., & Leonard, J. L. (1990). Thyroxine-dependent modulation of actin polymerization in cultured astrocytes. A novel, extranuclear action of thyroid hormone. The Journal of Biological Chemistry, 265, 5296–5302.

    PubMed  CAS  Google Scholar 

  • Silva, J. E. (2006). Thermogenic mechanisms and their hormonal regulation. Physiological Reviews, 86, 435–464.

    Article  CAS  PubMed  Google Scholar 

  • Spencer, C. A., Lum, S. M., Wilber, J. F., Kaptein, E. M., & Nicoloff, J. T. (1983). Dynamics of serum thyrotropin and thyroid hormone changes in fasting. The Journal of Clinical Endocrinology and Metabolism, 56, 883–888.

    Article  CAS  PubMed  Google Scholar 

  • St Germain, D. L., Galton, V. A., & Hernandez, A. (2009). Minireview: Defining the roles of the iodothyronine deiodinases: Current concepts and challenges. Endocrinology, 150, 1097–1107. https://doi.org/10.1210/en.2008-1588.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sugrue, M. L., Vella, K. R., Morales, C., Lopez, M. E., & Hollenberg, A. N. (2010). The thyrotropin-releasing hormone gene is regulated by thyroid hormone at the level of transcription in vivo. Endocrinology, 151, 793–801.

    Article  CAS  PubMed  Google Scholar 

  • Taylor, T., Gesundheit, N., & Weintraub, B. D. (1986). Effects of in vivo bolus versus continuous TRH administration on TSH secretion, biosynthesis, and glycosylation in normal and hypothyroid rats. Molecular and Cellular Endocrinology, 46, 253–261.

    Article  CAS  PubMed  Google Scholar 

  • Thijssen-Timmer, D. C., Schiphorst, M. P., Kwakkel, J., Emter, R., Kralli, A., Wiersinga, W. M., & Bakker, O. (2006). PGC-1alpha regulates the isoform mRNA ratio of the alternatively spliced thyroid hormone receptor alpha transcript. Journal of Molecular Endocrinology, 37, 251–257. https://doi.org/10.1677/jme.1.01914.

    Article  PubMed  CAS  Google Scholar 

  • Thompson, G. R., Soutar, A. K., Spengel, F. A., Jadhav, A., Gavigan, S. J., & Myant, N. B. (1981). Defects of receptor-mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo. Proceedings of the National Academy of Sciences of the United States of America, 78, 2591–2595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trost, S. U., et al. (2000). The thyroid hormone receptor-beta-selective agonist GC-1 differentially affects plasma lipids and cardiac activity. Endocrinology, 141, 3057–3064. https://doi.org/10.1210/endo.141.9.7681.

    Article  PubMed  CAS  Google Scholar 

  • Vaitkus, J. A., Farrar, J. S., & Celi, F. S. (2015). Thyroid hormone mediated modulation of energy expenditure. International Journal of Molecular Sciences, 16, 16158–16175. https://doi.org/10.3390/ijms160716158.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • van Marken Lichtenbelt, W. D., et al. (2009). Cold-activated brown adipose tissue in healthy men. The New England Journal of Medicine, 360, 1500–1508. https://doi.org/10.1056/NEJMoa0808718.

    Article  PubMed  Google Scholar 

  • Vansell, N. R., & Klaassen, C. D. (2001). Increased biliary excretion of thyroxine by microsomal enzyme inducers. Toxicology and Applied Pharmacology, 176, 187–194.

    Article  CAS  PubMed  Google Scholar 

  • Vansell, N. R., & Klaassen, C. D. (2002). Increase in rat liver UDP-glucuronosyltransferase mRNA by microsomal enzyme inducers that enhance thyroid hormone glucuronidation. Drug Metabolism and Disposition, 30, 240–246.

    Article  CAS  PubMed  Google Scholar 

  • Vella, K. R., & Hollenberg, A. N. (2009). The ups and downs of thyrotropin-releasing hormone. Endocrinology, 150, 2021–2023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vella, K. R., et al. (2014). Thyroid hormone signaling in vivo requires a balance between coactivators and corepressors. Molecular and Cellular Biology, 34, 1564–1575. https://doi.org/10.1128/MCB.00129-14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vella, K. R. et al. (2011) NPY and MC4R signaling regulate thyroid hormone levels during fasting through both central and peripheral pathways Cell Metabolism 14:780-790 doi:S1550–4131(11)00403–7 [pii] https://doi.org/10.1016/j.cmet.2011.126009.

  • Villicev, C. M., et al. (2007). Thyroid hormone receptor beta-specific agonist GC-1 increases energy expenditure and prevents fat-mass accumulation in rats. The Journal of Endocrinology, 193, 21–29. https://doi.org/10.1677/joe.1.07066.

    Article  PubMed  CAS  Google Scholar 

  • Visser, T. J. (1996). Pathways of thyroid hormone metabolism. Acta Medica Austriaca, 23, 10–16.

    PubMed  CAS  Google Scholar 

  • Weiss, R. E., Gehin, M., Xu, J., Sadow, P. M., O'Malley, B. W., Chambon, P., & Refetoff, S. (2002). Thyroid function in mice with compound heterozygous and homozygous disruptions of SRC-1 and TIF-2 coactivators: Evidence for haploinsufficiency. Endocrinology, 143, 1554–1557.

    Article  CAS  PubMed  Google Scholar 

  • Weiss, R. E., Xu, J., Ning, G., Pohlenz, J., O'Malley, B. W., & Refetoff, S. (1999). Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone. The EMBO Journal, 18, 1900–1904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wrutniak, C., et al. (1995). A 43-kDa protein related to c-Erb A alpha 1 is located in the mitochondrial matrix of rat liver. The Journal of Biological Chemistry, 270, 16347–16354.

    Article  CAS  PubMed  Google Scholar 

  • Wulf, A., Harneit, A., Kroger, M., Kebenko, M., Wetzel, M. G., & Weitzel, J. M. (2008). T3-mediated expression of PGC-1alpha via a far upstream located thyroid hormone response element. Molecular and Cellular Endocrinology, 287, 90–95. https://doi.org/10.1016/j.mce.2008.01.017.

    Article  PubMed  CAS  Google Scholar 

  • Yamada, M., et al. (1995). Activation of the thyrotropin-releasing hormone (TRH) receptor by a direct precursor of TRH, TRH-Gly. Neuroscience Letters, 196, 109–112.

    Article  CAS  PubMed  Google Scholar 

  • Yamada, M., et al. (1997). Tertiary hypothyroidism and hyperglycemia in mice with targeted disruption of the thyrotropin-releasing hormone gene. Proceedings of the National Academy of Sciences of the United States of America, 94, 10862–10867.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang, Z., & Privalsky, M. L. (2001). Isoform-specific transcriptional regulation by thyroid hormone receptors: Hormone-independent activation operates through a steroid receptor mode of co-activator interaction. Molecular Endocrinology (Baltimore, MD), 15, 1170–1185. https://doi.org/10.1210/mend.15.7.0656.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Weill Cornell Medical College, New York, NY, USA

    Kristen Rachel Vella

Authors
  1. Kristen Rachel Vella
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kristen Rachel Vella .

Editor information

Editors and Affiliations

  1. Emeritus Professor of Medicine, Molecular Biology, Cell Biology & Biochemistry, Department of Medicine, Molecular Biology, Cell Biology & Biochemistry, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA

    Eduardo A. Nillni

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Vella, K.R. (2018). The Thyroid Hormone Axis: Its Roles in Body Weight Regulation, Obesity, and Weight Loss. In: Nillni, E. (eds) Textbook of Energy Balance, Neuropeptide Hormones, and Neuroendocrine Function. Springer, Cham. https://doi.org/10.1007/978-3-319-89506-2_10

Download citation

Publish with us

Policies and ethics

Search

Navigation