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Endo > Growth hormone and IGF > Flashcards

Growth hormone and IGF Flashcards

1
Q

Where is GH released from?

A

Somatotropes of anterior pituitary

- aka somatotropin

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2
Q

What is GHRIH?

A

Growth hormone releasing inhiitory hormone

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3
Q

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

A
  • Promotes growth
  • Growing animals (especially bone growth if young enough)
  • Protein synthesis
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4
Q

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

A
  • Starvation response
  • Lipolysis
  • Insulin resistance (prevent storage and promote usage of nutrients)
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5
Q

What receptors do GH and IGF-1 bind to?

A
  • Cytokine receptors

- use JAK/STAT signalling pathway

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6
Q

Describe the growth response

A
  • 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
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7
Q

What triggers the starvation response and thus GH release?

A
  • Decreased lood glucose
  • Decreased blood free fatty acids
  • Decreased protein
  • Trauma, stress, excitement
  • Exercise
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8
Q

What are the slower, longer lasting hypertrophic actions mostly mediated by?

A

Insulin-like growth factors (some direct GF action but mostly IGF)

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9
Q

What are the physiological effects of GH in the starvation response?

A
  • 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
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10
Q

What is the effect of GH on the mammary glands?

A
  • Increased development in preparation for lactation

- In bitch leaks into system

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11
Q

Describe the normal physiological function of insulin-like growth factor-1

A
  • Mimic effects of insulin on growth
  • Stimulated by GH
  • Local (paracrine, autocrine) effects
  • Stimulate anabolism and growth
  • Increase chondrogenesis
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12
Q

Where is IGF-1 produced?

A

Different tissue, mainly liver

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13
Q

Describe the transport of IGF-1

A
  • Carrier proteins

- Increases half life leading to steady concentration of IGF-1

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14
Q

Describe the mechanisms by which IGF-1 exerts its actions

A
  • 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)
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15
Q

Describe the normal process of bone growth

A
  • 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
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16
Q

What is the result of excess GH while the bone plates are still open?

A
  • Extended bones

- Giantism

17
Q

What is the cause of pituitary dwarfism?

A
  • Deficient in growth hormone as a puppy
  • Spontaneous mutation
  • Hereditary
  • Most likely mutation of gene coding for transcription factor (LHX3)
18
Q

Describe the signalment for pituitary dwarfism

A
  • Spontaneous mutation (congenital): miniature Pinschers, Weimaraners, cats
  • Hereditary: GSD (autosomal recessive condition)
19
Q

What is the function of transcription factor LHX3?

A

Regulates pituitary stem cell differentiation

20
Q

What hormones are affected by pituitary dwarfism and why?

A
  • Decrease: GH, TSH, prolactin and gonadotrophins

- ACTH preserved as defect occurs after corticotrope differentiation

21
Q

Describe the clinical features o fpituitary dwarfism

A
  • 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)
22
Q

What are the physiological effects of giantism in humans?

A
  • 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
23
Q

What is acromegaly?

A

Pituitary disorders after closure of epiphyses leading to membranous bone growth

24
Q

What are the signs of acromegaly?

A
  • 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)
25
Q

Describe feline acromegaly

A
  • 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
26
Q

Describe canine acromegaly

A
  • 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
27
Q

What can be used to test for pituitary dwarfism?

A
  • Blood GH
  • Blood IGF
  • Dynamic pituitary stimulation test
28
Q

Discuss use of blood GH for pituitary dwarfism or acromegaly diagnosis

A
  • Pulsatile release
  • Low GH may be due to PD or normal peaks and troughs
  • Need species specific RIA
29
Q

Discuss blood IGF-1 for piuitary dwarfism or acromegaly diagnosis

A
  • 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
30
Q

Discuss the dynapic pituitary stimulation test for pituitary dwarfism diagnosis

A
  • 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
31
Q

How is acromegaly diagnosed?

A
  • 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)
32
Q

Describe the use of bovine somatotropin to increase milk production in dairy cows

A
  • 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

Endo (30 decks)

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