Growth Hormone

Question 1

How can protein hormone (ex: growth hormone) secretion be controlled?
(Hint: 3 general ways)

Answer 1

mRNA level: transcription, splicing
Protein level: cleavage, modification
Secretion level: stimulus, amount released from storage

Question 2

What brain structure synthesizes and secretes the growth hormone?

Answer 2

The anterior pituitary.

Question 3

How does growth hormone have a direct biological effect?

Answer 3

Metabolism: helps break down fatty acids and also synthesize protein.

Question 4

How does growth hormone have an indirect biological effect?

Answer 4

Growth: stimulates the liver (and other tissues) to produce IGF-1, promoting growth.

Question 5

How does growth hormone increase protein synthesis (as a direct effect)?

Answer 5

By increasing the amino acid uptake and accelerating transcription/translation of mRNA.

Question 6

What effect does growth hormone have on insulin?

Answer 6

Suppresses the ability of insulin to both stimulate glucose uptake in tissues and enhance glycogen synthesis in the liver.

Question 7

What 2 hormones are inhibited by somatostatin?

Answer 7

1. Growth hormone

2. Thyroid stimulating hormone

Question 8

What hormone stimulates the synthesis and release of growth hormone? What brain structure secretes this?

Answer 8

Stimulated by growth hormone releasing hormone, which is secreted from the hypothalamus.

Question 9

What tissue produces ghrelin? Where does this bind? What effect does this have on growth hormone?

Answer 9

Released from the stomach when empty. Binds to (secretagogue) receptors on somatotrophs and stimulates the secretion of growth hormone.

Question 10

How does the stimulation of IGF-1 by growth hormone have an effect on the growth hormone axis?

Answer 10

IGF-1 acts on the pituitary by negative feedback and also stimulates the production of somatostatin (inhibits growth hormone production).

Question 11

The release of growth hormone from the pituitary acts on the hypothalamus to inhibit the secretion of growth hormone releasing hormone by negative feedback. What other effect does this have?

Answer 11

It also acts by autocrine signalling in a negative feedback loop on itself.

Question 12

What can we do to cause an increase in growth hormone?

Answer 12

stress (from exercise) and sleep, as well as increased protein consumption.

Question 13

What can we do to cause a decrease in growth hormone?

Answer 13

Consume sugars and fats, or get old

Question 14

At what age do growth hormone levels generally drop in humans?

Answer 14

30 years old.

Question 15

How is growth hormone released (physically)? When during the day does the greatest release of growth hormone occur?

Answer 15

Released in a pulsatile patter, with the largest release coming just after the onset of deep sleep.

Question 16

How does the presence of thyroid hormone influence the effect of growth hormone? What about the other way around?

Answer 16

They exhibit cooperativity/synergy. Together they have a much greater effect than they would individually.

Question 17

Besides growth hormone deficiency, what else can lead to reduced growth?

Answer 17

Hypothyroidism can stunt growth even more than lack of growth hormone.

Question 18

How is tyrosine kinase associated with cytokine receptors?

Answer 18

The cytokine receptor does not have any integrated tyrosine kinase, but rather recruits accessory proteins with a tyrosine kinase domain.

Question 19

What kind of receptor does growth hormone bind to?

Answer 19

Cytokine receptors.

Question 20

In which 5 tissues is growth hormone receptor expressed?

Answer 20

1. Liver
2. Muscle
3. Bone
4. Kidney
5. Adipose tissue

Question 21

How does growth hormone move around the body?

Answer 21

In the bloodstream bound to growth hormone binding protein (for stability, specificity, etc.)

Question 22

What does growth hormone binding protein resemble (structurally)?

Answer 22

It’s actually just a growth hormone receptor without a membrane anchor (made by alternative splicing)!

Question 23

What is an interleukin?

Answer 23

A type of cytokine which binds to a similar receptor as growth hormone.

Question 24

How does the growth hormone receptor complex bind growth hormone?

Answer 24

Similar parts of the two receptor molecules bind two distinct regions on the growth hormone.

Question 25

What occurs to receptor binding of growth hormone when growth hormone is at high concentration? Why does this occur?

Answer 25

Growth hormones bind to only one receptor molecule each. This prevents dimerization (therefore signalling) because growth hormone needs to be bound to 2 diferent receptors to have an effect.

Question 26

How are growth hormone receptors and Janus-associated kinase 2 associated?

Answer 26

Janus-associated kinase 2 is recruited by the growth hormone receptors upon dimerization.

Question 27

What is the function of Janus-associated kinase 2 when it is recruited by growth hormone receptors?

Answer 27

It is a tyrosine kinase which phosphorylates itself, the receptor, and also signal transducer and activator of transcription (STAT)

Question 28

What occurs once Janus-associated kinase 2 phosphorylates STAT during growth hormone signalling?

Answer 28

Signal transducer and activator of transcription (STAT) forms a dimer, then migrates to nucleus and acts as a transcription factor for IGF-1.

Question 29

What amino acid plays an important role in both the phosphorylation of JAK2 and the binding of STAT to growth hormone receptors?

Answer 29

Tyrosine.

Question 30

What 3 pathways can phosphorylation of Janus-associated kinase 2 activate?

Answer 30

1. STATs
2. PI3K
3. MAPK

Question 31

What role does ubiquitin play in the growth hormone signalling pathway? What amino acid does it bind to in proteins?

Answer 31

Recycling and degradation of pathway elements by binding to lysine residues. Signals proteolysis.

Question 32

How do phosphatases work to downregulate the growth hormone pathway?

Answer 32

By dephosphorylating tyrosines on the receptor and associated proteins.

Question 33

What are SOCSs? How are they involved in growth hormone signalling?

Answer 33

Supressors of cytokine signalling. Can activate ubiquitin (for recycling) or inhibit kinase activity. Also targets JAK and STAT proteins for degradation.