Thyroid Hormones (Lecture 21)

Question 1

Describe the iodide pump mechanism from blood into the colloid, including the role of pendrin

Answer 1

• Iodide pump:
  
  • Sodium-iodide symporter (2:1) in basal membrane of thyroid cell
  • Engergy for pump comes form a sodium-potassium ATPase pump
  • Iodide can be concentrated insdie the cell 30-250x plasma concentration
  • Iodided is transported across apical membrane of cell into follicle via a chloride-iodide counter-transporter= pendrin
  • membrane enzyme, peroxidase,catalyzes conversion of iodide into iodine (I₂)

Question 2

Describe the synthesis of thyoid hormones

Answer 2

• Organification of iodine:
  
  • Combining of iodine with tyrosine on thyroglobulin
  • Catalyzed by peroxidase
  • Results in monoiodotyroisine (MIT) and diiodotyrosine (DIT)
• Recombination
  
  • DIT + DIT = Thyroxine (T₄)
  • DIT + MIT = triiodothyronine (T₃)

Question 3

Describe the mechanism for the release of thyoid hormones

Answer 3

• Apical surface of thyroid cells pinch off small portions of the follicular colloid to form pinocytic vesicles
• Lysosomes fuse with vesicles and digest thyroglobulin molecules to release thyroxine and triodothyronine (thyroid hormones)
• thyroid hormones diffuse into blood
• most of the iodinate tyrosine in the thyroglobulin does not become thyroid homrones but is recycled using a deiodinase enzyme
• Most of released thyroid hormone is thyroxine which then is slowly deiodinated to form triiodothyroine
• Conversion from T₄ to T₃ requires 5’ iodinase
• T₃ is more active than T₄
• Most thyroid hormones (T₄ and T₃) entering blood are immediately bound to plasma proteins synthesized in the liver
  
  • Thyroxin-binding gloulin (TBG)
    
    • produced by liver
    • Hepatic failure: decreased total thyroid hormone level but normal free hormone levels
• Plasma proteins have a high affinity for thyroid hormones, so the hormones are released slowly to tissue cells
  *

Question 4

List the physiological functions of thyroid hormones

Answer 4

• Increased transcription of a large number of genes
• Increased cellular metabolic activity
• effect on growth
• effects on specific bodily mechanisms:
  
  • Stimulation of carbohydrate metabolism
  • Stimulation of fat metabolism
  • Effect on plasma and liver fats
  • increased requirment for vitamins
  • increased BMR
  • Decreased body weight
• Effects on cardiovascular system:
  
  • Increased blood flow and cardiac output
  • increased heart rate
  • Normal arterial pressure
  • Increased respiration
• Increased GI motility
• Excitatory effects on CNS
• Effects on muscle function
• Muscle tremor
• effect on sleep
  
  • hyperthyroidism leads to difficulty sleeping
• Effect on other endocrine glands
  
  • increased thyroid hormone increases
• Effect on sexual function
  
  • Hypothyroid leads to decreased libido
  • hyperthyroidism leads to impotence

Question 5

Draw the pathway by which thyroid hormone activates target cells

Answer 5

Question 6

Relate thyroid hormone to BMR, hypothyroidism, and hyperthyroidism

Answer 6

• BMR increases with thyroid activity
  
  • normally BMR- 0
  • Hyperthyorid greater than 0
  • Hypothyroid negative BMR

Question 7

List factors that are involved in regulation of thyroid hormone secretion

Answer 7

• TSH
• cAMP
• TRH
• Cold and other neurogenic stimuli
• Thyroid hormone feedback

Question 8

Identify major hormonal product

Question 9

• List causes and symptoms of hyperthyroidism, including Graves’ disease

Answer 9

• Causes:
  
  • Grave’s disease
    
    • high concentrations of circulating thyroid-stimulating immunoglobulins:
      
      • IgG components
      • Mimic TSH and bind to TSH receptors
      • Result in high concentrations of circulating thyroxine and low levels of TSH
  • Adenoma
• Symptoms:
  
  • High state of excitability
  • Intolerance to heat
  • Increased sweating
  • Mild to extreme weight loss
  • Varying degress of diarrhea
  • Muscle weakness
  • Nervousness or other psychic disorders
  • Extreme fatigue
  • Inability to sleep
  • Tremor in hands
  • Exophthalmos

Question 10

• List causes and symptoms of hypothyroidism, including:
  
  • Hashimoto disease
  • Endemic goiter
  • Cretinism

Answer 10

• Causes:
  
  • Hashimoto disease (autoimmunity)
  • Endemic goiter
  • Cretinism (caused by extreme early hypothyroidism)
• Symptoms:
  
  • Generally opposite those of hyperthyroidism
  • Myxedema
  • Atherosclerosis

Question 11

Describe the concepts behind different therapies for thyroid disorders

Answer 11

• Thiocyanate and perchlorate anions:
  
  • Inhibit iodine uptake (inhibit I^- - Na⁺ cotransport)
• Propylthiouracil:
  
  • Inhibits peroxidase
  • can be used to treat for hyperthyroidism
• Iodides:
  
  • Decrease thyroid activity when present in very high concentrations