Growth Hormone

Question 1

How is growth hormone synthesized and how is it released?

Answer 1

Its synthesized from somatotropin polypeptide hormone. It follows a pulsatile synthesis and secretion with main burst being at night.

Question 2

What is some direct effects of growth hormone?

Answer 2

Hypertrophy: increase in size/volume of cells (increase bone thickness.
Stimulates cell production: increase rate of mitosis (increase in bone length)
Stimulates cell metabolism
Increase protein synthesis and fat breakdown for energy

Question 3

What is the indirect effect of growth hormone?

Answer 3

GH acts as a tropic hormone, stimulates liver’s production of somatomedins (being insulin-like growth factor 1)

Question 4

What is the relationship between GH and carbohydrate metabolism?

Answer 4

When GH is in excess, decrease CHO utilisation and impairs glucose uptake into the cells

Question 5

What is the MoA of GHRH?

Answer 5

GHRH stimulates GH secretion from somatotrophs. GHRH binds to Gs subunit of the GPCR on the somatotrophs. Activating adenylate cyclase. This leads to intracellular cAMP accumulation and activation of the catalytic subunit of PKA. PKA phosphorylates cAMP response element binding protein (CREB). CREB gets activated and Pit-1 activates transciption of the GH gene.

Question 6

What is the MoA of GH?

Answer 6

GH binds to a plasma membrane localised receptor. Activated GHR interacts with intracellular members of Janus Kinases. This leads to docking of STAT family to the GHR. Subsequent activation of the RAS and PI3K signal trasduction pathways.

Question 7

What is somatostatin (GHIH) MoA?

Answer 7

Binds to Gi receptors which leads to decreased activated of adenylate cyclase, intracellular cAMP, Ca [], stimulation of protein tyrosine phosphatase

Question 8

What is the relationship between GH and hypoglycaemia?

Answer 8

Low glucose stimulates the hypothalamus to secrete GHRH which stimulates anterior pituitary to release GH.

Question 9

List 5 factors that increase secretion of GH?

Answer 9

Hypoglycaemia, exercising, fasting, protein meal, glucagon, going to sleep and dopamine receptor agonists

Question 10

List 4 factors that inhibit secretion of GH

Answer 10

REM sleep, decreased amino acid levels, obesity, low TH levels, glucose increase.

Question 11

Whats the difference between acromegaly and gigantism?

Answer 11

Acromegaly - is in adults and its overgrowth of the skull and mandible. The epiphyses are closed so there is no growth of long bones.

Gigantism - occurs in childhood and adolescence, there is hypogonadism in these patients which delays epiphyseal closure.

Question 12

What are lab findings of acromegaly?

Answer 12

Elevated postprandial plasma glucose, increased serum insulin, hypercalciurea

Question 13

How do we diagnose acromegaly?

Answer 13

Measure basal fasting GH levels
Glucose supression test (OGTT)
IGF-1 measurements are elevated.

Question 14

What is the MoA of octerotide?

Answer 14

Mimics natural somatostatin by inhibiting serotonin release, and secretion of insulin, glucagon and vasoactive intestinal peptide. Its 45 times more potent than somatostatin

Question 15

What are adverse effects of octreotide?

Answer 15

Nausea, vomiting, steatorrhea, gallstones, use in caution in patients with heart failure, hepatic and renal impairment.

Question 16

What is the MoA of Pegvisomant?

Answer 16

Binds selectively to GH receptors, blocking the binding of endogenous GH. Its indicated to treat acromegaly in patients who have had an inadequate response to surgery or radiation.

Question 17

What is one major adverse effect of pegvisomant?

Answer 17

Decreased negative feedback by GH and IGF-1 may increase growth of GH secreting adenomas, monitor with MRI

Question 18

What is Turner syndrome?

Answer 18

It affects girls and women. Its a partially/missing X chromosome. Symptoms include short stature and lack of breast development and periods.