Growth hormone and IGF-1

Question 1

What is the source of growth hormone?

Answer 1

somatotropes in anterior pituitary

Question 2

Describe the regulation of GH release

Answer 2

Question 3

What are the long term effects of GH and IGF-1

Answer 3

promotes growth
- growing animals
- protein synthesis

Question 4

What are the short term effects of GH and IGF-1?

Answer 4

Starvation response:
- lipolysis
- insulin resistance

Question 5

Why can GH not be given orally?

Answer 5

Would be digested

Question 6

Describe the promotion of protein synthesis by GH and IGF-1

Answer 6

increased nuclear transcription
Increased translation
Increased AA transport through cell membrane
Decreased catabolism of proteins and AAs

Question 7

What is the stimulus for GH release?

Answer 7

Decreased blood glucose
Decreased blood free FAs
Decreased protein
Trauma, stress, excitement
Exercise

Question 8

Describe the physiologic effects of GH in the starvation response

Answer 8

Rapid catabolic actions => hyperglycaemia
Increased rate of protein synthesis
Increased lipolysis
Promotes hyperglycaemia:
- decreased glucose transport across cell membranes
- increased insulin antagonism
- increased gluconeogenesis

Question 9

Describe the features of IGF-1

Answer 9

Mimics effects of insulin on growth
Stimulated by GH
Produced mainly by liver
Bound to carrier proteins - increases half life

Question 10

Describe the effect of IGF-1 (somatomedin C)

Answer 10

• increases chondrocytes and osteogenic cell replication
• increase chondrocytes and osteogenic cell protein deposition to promote bone growth
• converts chondrocytes to osteoblasts to form new bone

Question 11

Describe bone growth

Answer 11

Open growth plates or epiphyseal cartilage
GH => increased cartilage deposition
GH => stimulates osteoblasts
Cartilage mineralises => increased bone length
Growth plates close
Epiphyseal cartilage fused to bone shaft (diaphysis)

Question 12

What is the mechanism of pituitary dwarfism?

Answer 12

Mutation of a gene coding for a transcription factor that regulates pituitary stem cell differentiation
Defect occurs after corticotrope differentiation (ACTH not affected)
Decreases GH, TSH, prolactin and gonadotropins
Can be accompanied by a cyst

Question 13

What are the clinical features of pituitary dwarfism?

Answer 13

proportionate growth retardation
Soft woolly hair coat:
- lack of primary hairs
Truncal alopecia
Lethargic
Decreased appetite
appear systemically ill

Question 14

What can occur secondary to pituitary dwarfism?

Answer 14

secondary hypothyroidism - thyroid hormones have a large impact on brain development

Question 15

What is the effect of pituitary dwarfism on reproductive function?

Answer 15

Decreased gonadotropins

Males:
- uni/bilateral crytorchidism

Females:
- persistent oestrus
- failure to ovulate (low P4)

Question 16

How is pituitary dwarfism diagnosed

Answer 16

Decreased IGF-1
Decreased GH (pulsatile so difficult to diagnose with this)
Dynamic pituitary stim test

Question 17

What are the effects of GH excess?

Answer 17

Giantism - develops in young patients before closure of epiphyses
Acromegaly - develops in adult patients after closure of epiphyses

Question 18

What is the cause of pituitary dwarfism?

Answer 18

congenital (spontaneous mutation)
hereditary in german shepherds

Question 19

What is the effect of giantism?

Answer 19

All tissue grow excessively
Hyperglycaemia (GH antagonises insulin)
Pancreatic failure due to overworking
Diabetes mellitus
Panhypopituitarism

Question 20

Describe the effects of acromegaly

Answer 20

Membranous bones continue to grow:
- broad coarsened facial feature
- prognathism (protrusion of mandible)
- nose
- feet (paw enlargement)
Increased facial soft tissues:
- increased soft tissue over eyes
- macroglossia (large tongue)
- increased interdental spaces
Internal organomegaly:
- heart
- liver
- kidneys

Question 21

What is the most common cause of feline acromegaly in cats?

Answer 21

pituitary tumour secreting excess GH

Question 22

Describe the diabetic appearance of cats with acromegaly

Answer 22

Acromegaly most common cause of insulin resistance in diabetic cats
Higher insulin doses required to treat diabetes due to GH causing insulin resistance

Question 23

What is the cause of acromegaly in dogs?

Answer 23

induction of GH gene in mammary glands (mammary GH identical to pituitary GH)

Question 24

Describe the diagnosis of acromegaly

Answer 24

IGF-1 concentration - reflects GH over last 24 hrs
GH concentration (pulsatile)
Dogs - history of natural or exogenous progesterone exposure
Cats - CT or MRI brain scan