Ellsworth RS 1- Growth Hormone

Question 1

What type of receptor does growth hormone bind to?

Answer 1

Tyrosine kinase receptor

Question 2

What are 5 stimulants of growth hormone?

Answer 2

Stimulants

• Deep sleep
• Fasting/hypoglycemia
• Estradiol
• Amino acids
• Ghrelin

Inhibitors
-Glucocorticoids, glucose, and IGF-1

Question 3

What are 3 inhibitors of growth hormone? How do they exhibit their effects?

Answer 3

Glucocorticoids inhibit growth hormone at the pituitary

Glucose decreases GH secretion

IGF-1 (somatomedins) Decreases GHRH and GH, as well as increases somatostatin

Question 4

What will the binding of growth hormone to its receptor stimulate the transcription of?

Answer 4

IGF1
IGFBP3
ALS

Question 5

What events occur after growth hormone releasing hormone (GHRH) binds to it’s receptor?

Answer 5

Growth hormone will bind to its tyrosine kinase receptor on somatotrophs and cause the activation PKA.

PKA will phosphorylate L-type calcium channels, which causes exocytosis of pre-formed growth hormone granules

PKA will also phosphorylate CREB, which causes the activation of this regulatory binding protein

CREB will activate POU1F1, which works on GH1 to increase the transcription of GH

Summary, through L-Type calcium channels, pre-formed growth hormone granules will be exocytosed, and POU1F1 transcription will be upregulated

Question 6

How is growth hormone binding protein (GHBP) related to the growth hormone receptor? How is GHBP made?

Answer 6

GHBP is the extracellular domain of the growth hormone receptor. If GH does not bind, it is cleaved and transports approximately 60% of GH, increasing its half-life.

Question 7

What are the direct and indirect effects of growth hormone on metabolism?

Answer 7

Direct effects: Increase lipolysis, increase blood sugar

Indirect effects: Through IGF-1, increase chondrogenesis, protein synthesis and muscle cell proliferation

Question 8

In what ways is IGF-1 transported in circulation? What percentage of IGF-1 is accounted for by each method? What is the half-life for each mechanism?

Answer 8

Free IGF-1 has a 10 minute half-life and accounts for 1% of all circulating 1GF-1

Binary complex: IGF1-IGFBP3. 30-90 minute half-life, accounts for 20-25% of all circulating IGF-1 . Can leave capillaries and activate IGF receptor, but not as well as free IGF-1

Ternary IGF-1: IGF-1/IGFBP3/ALS. 10-16 hour half-life. Cannot activate IGF receptor and prevents non-specific metabolic effects of IGFs, like severe hypoglycemia

Question 9

What are the two signal transduction pathways that IGF-1 will activate? What effects will they have?

Answer 9

PI3K/AKT- Decrease apoptosis, increase protein synthesis

MAPK- Increase proliferation

Question 10

What hormone is responsible for the closure of the epiphyseal plate during puberty?

Answer 10

Estradiol

Question 11

What test is done to measure growth hormone levels in the blood? What should the response be?

Answer 11

Insulin Tolerance Test

Insulin will cause hypoglycemia, and therefore GH levels should rise

Question 12

What are some pharmaceutical treatments for GH excess?

Answer 12

Somatostatin receptor agonists (Octreotide)

GH receptor antagonists (Pegvisomant)

Dopamine agonist (Bromocriptine)