Week 2. GH/IGF axis

Question 1

What type of hormone is Growth Hormone (GH)?

Answer 1

Peptide hormone

Question 2

What is another term for GH?

Answer 2

Somatotrophin

Question 3

Where is GH synthesised?

Answer 3

Anterior pituitary gland, in cells called somatotrophs

Question 4

How is GH production regulated?

Answer 4

Regulated in hypothalamus.

GH releasing hormone responsible for synthesis of GH.

GH inhibitory hormone (somatostatin) responsible for inhibition of GH synthesis.

GH is released into the blood in pulses.

Question 5

What is the function of GH and where does it act?

Answer 5

Target tissue is the liver.

Stimulates the production of insulin like growth factor 1 (IGF1). IGF one is released into the blood and ECF as it is produced and isn’t stored.

Question 6

Which IGF (1 or 2) is regulated by GH?

Answer 6

IGF1 only

Question 7

Which structure does IGF1 and IGF2 resemble?

Answer 7

Structure of insulin

Question 8

Outline the differences between IGF1 and IGF2 receptors

Answer 8

IGF1R binds both IGF1 AND IGF2. Structurally very similar to the insulin receptor.

IGF2R has no response to binding (no intracellular response).

Question 9

What are the cellular effects of GH through IGF1?

Answer 9

1. Mitogenic effect (induce cell proliferation).
2. Inhibit apoptosis (cell death).
3. Encourage cell differentiation.

Question 10

What are the metabolic effects of GH through IGF1?

Answer 10

Increases amino acid and glucose uptake in muscles.
- insulin like effects at high levels (high IGF1 levels: hypoglycaemia, low levels, hyperglycaemia)

Encourages protein synthesis, inhibits protein degradation
- leads to an increase in muscle mass

Question 11

What are the direct effects of GH?

Answer 11

Inhibits insulin stimulated lipogenesis.

Increases lipolysis, especially at low insulin concentrations.
- leads to a decrease in body fat

Question 12

What effects are observed when GH is given to individuals?

Answer 12

1. increased IGF1 levels
2. Increased growth (if well fed)
3. Increased lean (muscle, tendons)
4. Decrease in body fat
5. Increased liver weight
6. Increased insulin resistance

Question 13

What is the clinical significance of GH?

Answer 13

Excess GH before puberty = gigantism
Excess GH after puberty = acromegaly
GH deficiency = dwarfism

Question 14

Outline treatments for GH deficiency.

Answer 14

If the problem is GH production 
- regular injections of GH, mimicking the pulsatile release 
If the problem is GH receptors:
- regular IGF1 injections 
If the problem is IGF1R:
- very difficult to treat

Question 15

What are the major abnormalities associated with IGF1 deficiency in mice?

Answer 15

• postnatal death
• infertility
• differences in growth sizes: bigger brain, heart, liver, kidney
• intrauterine/postnatal growth retardation

Question 16

What are the effects of diet on the GH/IGF axis?

Answer 16

Fasting increases GH levels, but reduces IGF levels - less growth.
High carb/protein diet - reduces GH, increases IGF and growth.
- Strong positive correlation between protein and IGF levels. Protein levels key element of IGF axis.
Energy has no effect on IGF levels.

Question 17

When is GH usually released?

Answer 17

Diurnal secretion - secreted when sleeping or partially fasted.

Question 18

Outline the neonatal IGF axis.

Answer 18

levels in foetal blood
IGF1 - postnatal IGF - low levels in foetal blood

Postnatal switch from IGF2 to IGF1
- cortisol surge triggers switch

Question 19

What is the relationship between IGF1 and age?

Answer 19

IGF1 reduces as we age, and peaks at the ages of 15-20.