Growth Hormone

Question 1

What is the role of GHRH in GH expression?

Answer 1

Increases GH gene transcription
Promotes GH release
Stimulates production of GHRH receptors
Stimulates somatostatin release– Neg feedback

Question 2

What is the role of somatostatin in GH expression?

Answer 2

Decreases pulse frequency and amplitude
No impact on GH synthesis
Inhibits GHRH release

Question 3

What is the role of Ghrelin in GH expression?

Answer 3

Acts on growth hormone secretion receptor

Important during times of fasting/starvation

Question 4

When is GH secretion the greatest?

Answer 4

Right after strenuous exercise and first few hours of deep sleep

Question 5

ADHD medications such as Ritalin do what to children?

Answer 5

Interrupt deep sleep and cause stunted growth

Question 6

What stimulates GH secretion?

Answer 6

Deep sleep
Exercise
Sex steroids
Fasting--hypoglycemia
Amino acids--arginine--decrease somatostatin release
Stress
a-andrenergic agonist
Dopamine agonists

Question 7

What inhibits GH secretion?

Answer 7

IGF-I
Obesity
Glucocorticoids
Hyperglycemia
Free fatty acids
GH
B-adrenergic agonists

Question 8

How does growth hormone activate its receptors?

Answer 8

Binding of GH changes arrangement of receptor dimer and activates JAK2–phosphorylates/activates STAT transcription factors for GH

Question 9

How is GH released from the somatotrphic cells in the anterior pituitary?

Answer 9

GHRH reaches the somatotroph cell in the anterior pituitary via long portal veins–stimulates Gs protein-coupled receptors–raises cAMP—activating PKA to phosphorylate the transcription factor CREB–upregulates Pit-1–increasing GH and GHRH receptors–PKA also increases Ca which leads to secretion of GH

Question 10

How does somatostatin inhibit GH release from the anterior pituitary?

Answer 10

Somatostatin is released from the hypothalamus and goes to the anterior pituitary through long portal veins–work through Gi-protein coupled receptors inhibiting adenylyl cyclase and lowers [Ca]

Question 11

What does GH stimulate in the liver and what does this effect?

Answer 11

IGF-1 production– stimulates hepatic glucose production

Also IGF-1 inhibits GH release

Question 12

What does GH stimulate in Adipose tissue and how is this mediated?

Answer 12

Stimulates release and oxidation of Free fatty acids particularly during fasting

Mediated by reduction of activity of lipoprotein lipase

Question 13

What does GH stimulate in skeletal muscle?

Answer 13

Anabolic action on skeletal muscle–stimulates amino acid uptake and incorporation into protein and cell proliferation–increases metabolism

Question 14

What are high levels of GH going to cause?

Answer 14

blocking action of insulin–GH counteracts the affects of insulin–increases lipolysis and stimulates glucose production

Question 15

What does IGF-1 induce in bone development?

Answer 15

clonal expansion of the early chondrocytes and maturation of later chondrocytes—leads to synthesis of extracellular matrix proteins

Question 16

What 2 things are needed for the production of IGF-1?

Answer 16

GH and Food

Question 17

What does GH do to insulin secretion and its action?

Answer 17

increases insulin secretion BUT blocks its action

Question 18

Once IGF-1 binds its receptor what occurs?

Answer 18

Dimerization which leads to autophosphorylation

Question 19

Autophosphoylation of the IGF-1 receptor cause what to occur?

Answer 19

recruits two major phosphotyrosine binding proteins–IRS-1 and Shc

Question 20

After phosporylation of IRS-1 and Shc on the IGF-1 receptor what occurs?

Answer 20

Activation of PI3K and Ras/MAP kinase pathway–which regulate cellular transcription

Question 21

What does the pubertal peak rate of growth correspond with?

Answer 21

serum [IGF-1]

Question 22

What is Laron syndrome and what causes it? What is seen clinically with these pts? How is it treated?

Answer 22

Growth hormone insensitivity cause by point mutation or deletion in GH receptor

Low [IGF-1]
Normal-elevated [GH]
severe post-natal growth

Treatment– rhIGF-1

Question 23

What is Acromegaly and what causes it?

Answer 23

Increase in GH caused by adenomas—causes protrusion of the jaw/macroglossia(large tongue)/enlarged hands and feet/carpal tunnel syndrome/reduced strength

Question 24

GH deficiency causes an increase in what and decrease in what?

Answer 24

Increase- visceral adipose tissue/clotting factors/insulin resistance-LDL

Decrease- myocardial function

Question 25

What happens to GH when aging and what happens due to this?

Answer 25

Decrease in GH levels–contribute to some normal effects of aging such as loss of muscle mass and increase in interstitial body fat

Question 26

What can cause decreased levels of GH in children and stunted growth?

Answer 26

Celiac dz and hypothyrodism

Question 27

What causes short stature in turner syndrome pts?

Answer 27

Attributed to SHOX gene–SHOX gene is on X chromosome and with turners there is only 1 X so there is less SHOX gene which is important for growth development

Question 28

Why are Klinefelter’s syndrome Pts taller than normal?

Answer 28

SHOX gene located on the X chromosome that is developmentally regulated–also they have gonadotropin deficiency.

Pts don’t go into puberty and don’t fuse bones–continue to grow longer than normal