7. Endocrine System 3

Question 1

What is TSH, what controls its release and what does it affect?

Answer 1

1. Thyroid stimulating hormone
2. Controlled by the TRH (thyrotrophin releasing hormone)
3. TSH is a glycoprotein hormone that increases the rate of thyroxine (T4) and triiodothyroine (T3) secretion by the thyroid gland.

Question 2

Describe the formation of thyroid hormone in the thyroid gland and indicate the effect TSH has on the various steps in the process.

Answer 2

1. Transport of iodides from the blood to the thyroid glandular cells and follicles - ‘iodide trapping’
   - iodide pump is activated by TSH
2. endoplasmic reticulum and Golgi apparatus synthesize and secrete into the follicles the glycoprotein thyroglobulin
3. oxidation of the iodide ion
   - once oxidized capable of binding to tyrosine
   - promoted by the enzyme peroxidase and its accompanying hydrogen peroxide (peroxidase is found in the apical membrane of the cell or attached to it)
4. ‘organification’ of thyroglobulin
   - binding of iodine with the thyroglobulin
   - iodinase enzyme - rapidly binds iodine with 1/6th of the tyrosine amino acids in the thyroglobulin
   - successive stages of iodination
   - TSH increases iodination

Question 3

Why is there a latent response to thyroid hormone?

Answer 3

Due to extensive binding of thyroid hormones to plasma proteins (TBG), creating a gradual and sustained release.

Question 4

Describe the feedback effect of thyroid hormone on the anterior pituitary.

Answer 4

• It decreases the anterior pituitary secretion of TSH
  1. When levels of T4 and T3 in the bloodstream rise, they act on the anterior pituitary to reduce the secretion of TSH.
  2. A decrease in the production and release of T4 and T3 by the thyroid gland.
  3. As thyroid hormone levels fall, the negative feedback on the anterior pituitary lessens, allowing TSH secretion to rise again

Question 5

5. How are thyroid hormones deactivated?

Answer 5

1. Deiodinated in the liver, kidneys and other tissues
2. Conjugated in the liver to form sulfates and glucuronides
   - These conjugates enter the bile and pass into the intestine
   - Iodine is reabsorbed by the enterhepatic circulation

Question 6

What role does ACTH play in cortisol production?

Answer 6

ACTH from the anterior pituitary targets the adrenal cortex, specifically stimulating cortisol production by activating the cAMP pathway and cholesterol conversion in adrenal cells.
- Increases the rate of cortisol secretion by the adrenal gland

Question 7

As with TSH cortisol binds with plasma proteins. What is the value of having cortisol bound to proteins?

Answer 7

1. Protect cortisol from kidney excretion and liver inactivation
2. Water solubility
3. Dynamic storage
4. Regulate hormone availability to effector tissues

Question 8

Describe the effect of cortisol on carbohydrate

Answer 8

1. Increased glycogen in liver
   - Stimulates gluconeogenesis by liver
   - Increases the enzyme required to convert amino acids to glucose via formation of mRNAs
   - Causes mobilization of amino acids from the extrahepatic tissues – mainly muscle
2. Decreased utilization of glucose by cells
   - Depress oxidation of NADH to NAD+
3. See overall increase in blood glucose
   - Increased insulin but animal is somewhat insulin resistant

Question 9

Describe the effect of cortisol on fat

Answer 9

1. Promotes mobilization of fatty acids from adipose tissue
2. Increased oxidation of fatty acids in the cells
3. Leads to long term conservation of body glucose and glycogen
4. Redistribution of fat
   - See fat in neck, shoulder and abdomen not extremities (dogs and humans)
   - Accumulation of suborbital fat (horse)

Question 10

Describe the effect of cortisol on protein metabolism

Answer 10

1. Decreased cellular proteins
   - All cells except liver
   - Decreased protein synthesis and increased catabolism
   - Especially in muscle and lymphoid tissue
2. Increased liver and plasma proteins

Question 11

List four ways in which cortisol acts as an anti-inflammatory agent

Answer 11

1. Stabilizes the lysosomal membranes
2. Decreases permeability of capillaries
3. Decreases migration of white blood cells into area and decreases phagocytosis
4. Suppresses immune system
5. Reduces fever

Question 12

Describe feedback control of cortisol levels.

Answer 12

1. stress triggers CRF release from the hypothalamus
2. leads to ACTH release from the anterior pituitary
3. stimulating cortisol production.
4. High cortisol levels inhibit CRF and ACTH.

Question 13

Describe the deactivation of thyroid hormone.

Answer 13

1. Conjugated in the liver to form sulfates and glucuronides
2. These conjugates enter the bile and pass into the intestine
3. Conjugates are highly soluble in plasma and are therefore readily excreted by kidney