The thyroid gland

Question 1

What are the cells types of the thyroid gland?

Answer 1

○ C (clear) cells: secretes calcitonin (calcium regulating hormone)
○ Follicular cells
- support thyroid hormone synthesis and surround hollow follicles
- Manufacture the enzymes that make thyroid hormones
- Also makes thyroglobulin: a large protein rich in tyrosine residues
- The enzymes and thyroglobulin are packaged into vesicles and exported to the colloid
- Concentrate iodide from the plasma and transport it into the colloid where it combines with tyrosine residues to form the thyroid hormones

Question 2

Explain thyroid follicles

Answer 2

○ Spherical structures
○ Walls composed of follicular cells
○ Centre follicle filled with colloid (sticky glycoprotein matrix)
○ Contains 2-3 months supply of TH

Question 3

Describe the production of T3 and T4

Answer 3

○ The reaction is catalysed by thyroid peroxidase located on the apical membrane of the follicular cells
○ Iodide enters the follicular cells from the plasma via sodium iodine transporter (symport)
○ The coupling to sodium enables the follicular cells to take up iodide against a concentration gradient
○ Iodide is then transported into the colloid via the pendrin transporter
○ Iodide transport into the thyroid gland is inhibited by thiocyanates which are compounds from detoxification of cyanide (common origin is cigarette smoke)
○ Enzymes present in the colloidal side of the cells which catalyses the addition of iodide to tyrosine residues in thyroglobulin
○ The addition of one iodine to a tyrosine results in a MIT (mono-iodide tyrosine)
○ Adding another iodine results in DIT (di-iodide tyrosine)
○ When MIT and DIT combine you get triiodothyronine (T3)
○ When two DITs combine you get thyroxine (T4)

Question 4

Describe the secretion of T3 and T4

Answer 4

○ In response to TSH, portions of the colloid are taken up into the follicular cells by endocytosis
○ Within the cells they form vesicles which contain proteolytic enzymes that cut the thyroglobulin to release thyroid hormones
○ T3 and T4 are both lipid soluble and so pass across the follicular cell membrane into the plasma, where they bind to plasma proteins, mainly thyroxine-binding globulin
○ Both T3 and T4 circulate in the plasma

Question 5

Describe the T3/T4 ratio in thyroid secretion, protein binding of T4 and 3 in plasma, conversion of T4 into T3 in target tissues, and the significance attributed to these

Answer 5

• 50x more total (free + bound) T4 is in the plasma than T3
• However, 90% of the TH binding to the TH receptors inside the cells is T3
• The receptor has a greater affinity to T3 than T4 making T3 3-5 times more physiologically active than T4
• T4 is deiodinated to T3 by deiodinase enzymes
○ Around half the T4 is deiodinated to T3 in the plasma
○ The remaining fraction is deiodinated inside the target cells
○ The level of deiodinase activity can be altered at different times in different tissues to suit demand
• GC inhibits TSH and conversion T4 to T3
• SS inhibits TSH

Question 6

Describe the location of T3 receptors

Answer 6

Nuclear receptors that are inside the target cells

Question 7

Summarise the main actions of T3 and relate them to biological effects in humans

Answer 7

• They change transcription and translation to alter protein synthesis
○ Raises metabolic rate and promotes thermogenesis
○ Increases hepatic gluconeogenesis
○ Net increase in proteolysis
○ Net increase in lipolysis
○ Critical for growth (the lack of TH results in stunted growth)
- Anabolic
- Stimulates GH receptor expression
○ Required for foetal brain development (deficiency= congenital hypothyroidism)
- Can be caused by dietary deficiency