Question 14

 Describe the production, action and regulation of thyroid hormones

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College Answer

This question was divided in three sections to help candidates formulate an answer template, which for the most part was answered well. Most answers included a detailed description of the production and regulation of thyroid hormones, including the importance of negative feedback. A brief description of the action of thyroid hormones on intracellular receptors, and a system-based description of physiological effects, including CHO, protein and fat metabolism was expected.

Discussion

  • Synthesis of thyroid hormones
    • Iodine is absorbed from diet as iodide and concentrated by 30-40 times in the thyroid  follicles by the sodium/iodide symporter (NIS)
    • Thyroglobulin is then iodinated by the actions of thyroid peroxidase
    • Iodinated thyroglobulin is stored, and reabsorbed as needed by follicular cells
    • Proteolysis of thyroglobulin liberates T3 and T4 molecules
  • Circulation of thyroid hormones
    • Released thyroid hormones consist of 80% T4 and 20% T3
    • Circulating T4 and T3 are highly protein bound to thyroid hormone-binding globulin, a chaperone protein in the plasma 
    • T4 has a longer half life (6-7 days), gradually converted to T3 by peripheral deiodinase enzymes (ubiquitous, but mainly in the liver and kidneys)
    • T3 has a shorter half life (hours) and is the main biologically active thyroid hormone
  • Actions of thyroid hormones
    • Bind to mainly nuclear receptors, which act as transcription factors, modifying protein synthesis (though there are also cytosolic and membrane receptors)
    • Most physiologically important actions are mediated by gene transcription and therefore take more than 24hrs to manifest
    • Actions of thyroid hormones include:
      • Increased cardiac output due to increased contractility, and decreased peripheral vascular resistance)
      • Increased sympathetic nervous system activity, increased sensitivity to catecholamines
      • Psychological and neurodevelopmental effects
      • Increased renal blood flow and increased clearance rate of renally cleared substances
      • Increased hepatic protein synthesis and increased hepatic blood flow, with increased clearance rate of substances metabolised by the liver
      • Increased gastrointestinal motility and increased appetite
      • Increased blood flow to skeletal muscle
      • Increased shivering and nonshivering thermogenesis
      • Increased total body metabolic rate and oxygen consumption:
        • Increased gluconeogenesis increased hepatic glucose output
        • Decreased efficiency of mitochondrial electron transport, resulting in heat production
        • Increased lipolysis in white adipose tissue, ncreased free fatty acid release, increased hepatic lipogenesis, and increased use of lipids as metabolic fuel substrate
        • Reverse cholesterol transport
  • Regulation of thyroid hormones
    • Release of TRH is stimulated by low T4/T3 levels and cold temperature
    • TRH stimulates TSH release (which is inhibited by high T4/T3 levels, as well as somatostatin, dopamine and cortisol)
    • TSH stimulates T3 and T4 release
    • Conversion of T4 into T3 is also controlled by regulation of peripheral deiodinase activity

References

Stathatos, Nikolaos. "Thyroid physiology." Medical Clinics 96.2 (2012): 165-173.

Stathatos, Nikolaos. "Anatomy and physiology of the thyroid gland." The thyroid and its diseases. Springer, Cham, 2019. 3-12.

Maenhaut, C., et al. "Ontogeny, anatomy, metabolism and physiology of the thyroid." Endotext [Internet] (2015).