Growth hormone and IGF-1 Flashcards
What is the source of growth hormone?
somatotropes in anterior pituitary
Describe the regulation of GH release
What are the long term effects of GH and IGF-1
promotes growth
- growing animals
- protein synthesis
What are the short term effects of GH and IGF-1?
Starvation response:
- lipolysis
- insulin resistance
Why can GH not be given orally?
Would be digested
Describe the promotion of protein synthesis by GH and IGF-1
increased nuclear transcription
Increased translation
Increased AA transport through cell membrane
Decreased catabolism of proteins and AAs
What is the stimulus for GH release?
Decreased blood glucose
Decreased blood free FAs
Decreased protein
Trauma, stress, excitement
Exercise
Describe the physiologic effects of GH in the starvation response
Rapid catabolic actions => hyperglycaemia
Increased rate of protein synthesis
Increased lipolysis
Promotes hyperglycaemia:
- decreased glucose transport across cell membranes
- increased insulin antagonism
- increased gluconeogenesis
Describe the features of IGF-1
Mimics effects of insulin on growth
Stimulated by GH
Produced mainly by liver
Bound to carrier proteins - increases half life
Describe the effect of IGF-1 (somatomedin C)
- 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
Describe bone growth
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)
What is the mechanism of pituitary dwarfism?
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
What are the clinical features of pituitary dwarfism?
proportionate growth retardation
Soft woolly hair coat:
- lack of primary hairs
Truncal alopecia
Lethargic
Decreased appetite
appear systemically ill
What can occur secondary to pituitary dwarfism?
secondary hypothyroidism - thyroid hormones have a large impact on brain development
What is the effect of pituitary dwarfism on reproductive function?
Decreased gonadotropins
Males:
- uni/bilateral crytorchidism
Females:
- persistent oestrus
- failure to ovulate (low P4)
How is pituitary dwarfism diagnosed
Decreased IGF-1
Decreased GH (pulsatile so difficult to diagnose with this)
Dynamic pituitary stim test
What are the effects of GH excess?
Giantism - develops in young patients before closure of epiphyses
Acromegaly - develops in adult patients after closure of epiphyses
What is the cause of pituitary dwarfism?
congenital (spontaneous mutation)
hereditary in german shepherds
What is the effect of giantism?
All tissue grow excessively
Hyperglycaemia (GH antagonises insulin)
Pancreatic failure due to overworking
Diabetes mellitus
Panhypopituitarism
Describe the effects of acromegaly
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
What is the most common cause of feline acromegaly in cats?
pituitary tumour secreting excess GH
Describe the diabetic appearance of cats with acromegaly
Acromegaly most common cause of insulin resistance in diabetic cats
Higher insulin doses required to treat diabetes due to GH causing insulin resistance
What is the cause of acromegaly in dogs?
induction of GH gene in mammary glands (mammary GH identical to pituitary GH)
Describe the diagnosis of acromegaly
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
