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