The thyroid gland

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The thyroid gland

  • largest pure endocrine gland
  • well vascularised
  • located in the neck below the larynx
  • has two loves joined by a thin band (isthmus)
  • the only endocrine gland that stores its hormones in an extracellular compartment
  • composed of more than one million spherical follicles if varying sizes
  • blood vessels and lymph vessels exist between follicles
  • follicles separated by basement membrane
  • single layer of cells
  • the follicular cells synthesise thyroxine (T4) and triiodothyronine (T3)
  • these are amine hormones derived from the amino acid tyrosine
  • T4 contains four iodine molecules
  • T3 contains three iodine molecules
  • T3 and T4 are synthesised on a backbone of thyroglobulin, a large protein that is made within the follicular cells
  • synthesis of the thyroglobulin polypeptide chain, including addition of tyrosine molecules takes place in the rough endoplasmic reticulum of the cell; carbohydrate is added later in the Golgi body
  • thyroglobuin is secreted into the follicular lumen where it is stored in the colloid
  • the colloid is essentially a store of thyroglobulin

Iodide uptake into the follicular cells

  • iodine cannot be synthesised by the body but must be obtained in the diet
  • iodide is co-transported with sodium ions from the extracellular fluid into the follicular cells
  • sodium ions are pumped back out of the cell by the Na/K ATPase pump, which maintains the concentration gradient
  • iodide diffuses into the colloid along a concentration gradient 

Iodination of thyroglobulin

  • free iodine in the follicular lumen rapidly attaches itself to the tyrosine residues on the thyroglobulin molecules in a process called iodination
  • iodination occurs at the apical membrane (colliod-facing) membrane and involves hydrogen peroxide and oxidation by the enzyme thyroid peroxidase

Coupling to form iodotyrosines to form T4

  • thyroid peroxidase adds two iodine molecules to thyroglobulin to form diiodotyronise (DIT)
  • thyroid peroxidase then joins two DITs to form T4

Coupling of iodotyrosines to form T3

  • thyroid peroxidase adds one iodine molecule to thyroglobulin to form monoiodotyrosine (MIT)
  • thyroid peroxidasejoints one DIT and one MIT to form T3

Secretion of thyroid hormone

  • colloid and iodinated thyroglobulin is reabsorbed into the thyroid cells by endocytosis
  • thyroglobulin is broken down by lysosomes containing hydrolytic enzymes to release T4 and T3
  • T4 and T3 are released into the bloodstream
  • the thyroid secretes mainly T4, however T4 is a relatively inactive hormone which is converted to T3 (more active form) in the peripheral tissues by iodinase enzymes
  • about half of the T4 output is converted to reverse T3 which is inactive
  • T4 is more stable than T3, with a longer half-life; T3 is degraded by deiodination in the tissues or by conjugation in the liver
  • once secreted, over 90% of thyroid hormones are rapidly bound to plasma proteins
  • 70% is bound to thyroxine binding globulin (TBG)
  • 30% is bound to thyroxine binding pre-albumin (TPBA) and albumin (a general carrier protein)
  • only 0.4% of T3 and 0.04% of T4 are not bound to proteins
  • it is only the free fraction of T3 that is responsible for hormonal activity

Action of thyroid hormones

  •  action is via…


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