ENI - Growth hormone and IGF Flashcards
Where is GH released from?
Somatotropes of anterior pituitary
- aka somatotropin
What is GHRIH?
Growth hormone releasing inhiitory hormone
What are the long term effects of GH and IGF-1?
- Promotes growth
- Growing animals (especially bone growth if young enough)
- Protein synthesis
What are the short term effects of GH and IGF-1?
- Starvation response
- Lipolysis
- Insulin resistance (prevent storage and promote usage of nutrients)
What receptors do GH and IGF-1 bind to?
- Cytokine receptors
- use JAK/STAT signalling pathway
Describe the growth response
- Promotes protein synthesis
- Increase nuclear transcription (DNA to RNA)
- Increased translation (RNA to proteins)
- Increased AA transport through cell membrane
- Decreased catabolism of proteins and AAs
- Stimulation of differentiation of chrondrocytes and producton of IGF-1 to stimulate body growth
What triggers the starvation response and thus GH release?
- Decreased lood glucose
- Decreased blood free fatty acids
- Decreased protein
- Trauma, stress, excitement
- Exercise
What are the slower, longer lasting hypertrophic actions mostly mediated by?
Insulin-like growth factors (some direct GF action but mostly IGF)
What are the physiological effects of GH in the starvation response?
- Rapid catabolic actions (leading to hyperglycaemia)
- Protein: increased rate of synthesis
- Lipid: enhanced fat use, increased lipolysis
- Carbohydrate: promotion of hyperglycaemia, decreased glucose transport across cell membrane, increase insulin antagonism, increased gluconeogenesis
What is the effect of GH on the mammary glands?
- Increased development in preparation for lactation
- In bitch leaks into system
Describe the normal physiological function of insulin-like growth factor-1
- Mimic effects of insulin on growth
- Stimulated by GH
- Local (paracrine, autocrine) effects
- Stimulate anabolism and growth
- Increase chondrogenesis
Where is IGF-1 produced?
Different tissue, mainly liver
Describe the transport of IGF-1
- Carrier proteins
- Increases half life leading to steady concentration of IGF-1
Describe the mechanisms by which IGF-1 exerts its actions
- Increases chondrocytes and osteogenic cell replication
- Increase chondrocytes and osteogenic cell protein deposition to promote bone growth
- Convert chondrocytes to osteoblasts and form new bone (mineralisation of bone structures)
Describe the normal process of bone growth
- Open growth plates or epiphyseal cartilage
- GH causes increased cartilage deposition
- GH stimulates osteoblasts
- cartilage then mineralises, increasing bone length
- Meet in middle to close growth plates
- Epiphyseal cartilage fused to bone shaft
What is the result of excess GH while the bone plates are still open?
- Extended bones
- Giantism
What is the cause of pituitary dwarfism?
- Deficient in growth hormone as a puppy
- Spontaneous mutation
- Hereditary
- Most likely mutation of gene coding for transcription factor (LHX3)
Describe the signalment for pituitary dwarfism
- Spontaneous mutation (congenital): miniature Pinschers, Weimaraners, cats
- Hereditary: GSD (autosomal recessive condition)
What is the function of transcription factor LHX3?
Regulates pituitary stem cell differentiation
What hormones are affected by pituitary dwarfism and why?
- Decrease: GH, TSH, prolactin and gonadotrophins
- ACTH preserved as defect occurs after corticotrope differentiation
Describe the clinical features o fpituitary dwarfism
- Proportionate growth retardation
- Soft wooly hair coat: lack primary hairs, retention of secodnary hairs, easily epilated, truncal alopecia, areas of wear
- Hyperpigmentation of skin under alopecia
- Initially bright and alert, become lethargic, decreased appetite, appear systemically ill (secondary hypothyroidism)
- Males: uni/bilateral cryptorchidism
- Female: persisten oestrus, failure to ovulate (low progesterone)
What are the physiological effects of giantism in humans?
- All tissues grow excessively
- Hyperglycaemia
- Pancreatic failure (overwork)
- Diabetes mellitus
- Panhypopituitarism (complete failure as GH secreting tumour growth destroying other functions)
- Not documented in dog or cat
What is acromegaly?
Pituitary disorders after closure of epiphyses leading to membranous bone growth
What are the signs of acromegaly?
- Feet/paw enlargement
- Increased facial soft tissues (broad, coarsened facial features, increased soft tissue over eyes)
- Enlargeed tongue
- Increased interdental spaces
- Internal organommegaly (heart, liver, kidneys)
Describe feline acromegaly
- Middle age- old cats
- 90% males
- Pituitary tumour secreting excess GH
- Diabetic at presentation (common cause of insulin resistance in diabetic cats)
- Increased soft tissue around pharynx means increased respiratory effort which can lead to tracheal collapse
Describe canine acromegaly
- Middle aged-old dogs
- 100% female
- Excess endogenous progesterone due to dioestrus
- Or exogenous where used to suppress oestrus
- Induction of GH gene in mammary glands
- mammary GH identical to pituitary GH, leaks out into circualtion
What can be used to test for pituitary dwarfism?
- Blood GH
- Blood IGF
- Dynamic pituitary stimulation test
Discuss use of blood GH for pituitary dwarfism or acromegaly diagnosis
- Pulsatile release
- Low GH may be due to PD or normal peaks and troughs
- Need species specific RIA
Discuss blood IGF-1 for piuitary dwarfism or acromegaly diagnosis
- Decreased in PD
- Longer half life than GH adn no pulsatile secreiton
- Less species-specific AA sequence so can use human assay
- Preferred test
- Secretion in response to GH but is a more steady concentration so give an “average” GH
Discuss the dynapic pituitary stimulation test for pituitary dwarfism diagnosis
- Baseline blood sample, inject GH stimulant (GHRH, alpha-adrenergic drugs)
- Second sample 20-30 mins later
- Healthy dogs should have increased GH by 2-4x and hyperglycaemia due to GH
- PD dog has no increase in GH has pituitary is non-functional
How is acromegaly diagnosed?
- IGF-1 concetration
- GH concentration
- Supportive clinical signs and labwork with normal thyroid/adrenal testing
- History of natural or exogenous progesterone exposure (dogs)
- CT or MRI brain scan (cats)
Describe the use of bovine somatotropin to increase milk production in dairy cows
- Not legal in EU
- GH plays role in galactopoeisis as lactation progresses
- Partitions additional nutrient to mammary cell
- Increases sythesis of lactose, milk proteins and mmilk fat
- Antagonises actions of insulin
- Inhibits lipogenesis n adipose tisue and stimulates HSL, mobiising fatty acids from adipose tissue
- Stimulates appetite
