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19 Cards in this Set

  • Front
  • Back
How is GH secretion regulated?
1. GH secretion is pulsatile and episodic
2. GH secretion is enhanced by:
> exercise
> stress
> sleep (stages 3 and 4)
> postprandial decline in glucose levels
> increase in specific amino acids
3. GH secretion is inhibited by
> postprandial hyperglycaemia
> free fatty acids
What does postprandial mean?
Time after any meal
Describe GH secretion across life.
- Very high in mid-fetal life (up to 150ng/mL)
- 30ng/mL in cord blood
- 5-10ng/mL in children
- 2-5 ng/ml in young adults
- low in old age
What are the actions of GH?
- GH acts at specific GH receptors
- The biological activity of GH is regulated by a GH binding protein which is formed from the extracellular domain of the GH receptor
- The actions of GH are often mediated via a second molecule known as somatomedin, or more usually as IGF-1
- The actions of GH are anabolic and anti-catabolic, resultin gin increases in protein synthesis
Give a summary of the GH mechanisms of action.
- Direct Anti-insulin effects
> increased lipolysis
> increased glucose mobilization
- Indirect growth promoting effects
> increased cartilage formation
> increased long bone growth
> increased protein synthesis
Describe IGFs and Feedback.
- Indirect effects of GH are mediated by somatomedins
- Mostly IGF1 postnatally
- GH stimulate IGF1 production by
> liver (endocrine mechanism)
> GH target tissues (paracrine mechanism)
- IGF1 is bound in blood to one of 6 IGFBPs
- IGF1 feedback inhibits GH release at
> anterior pituitary
> hypothatlamus
What is the somatomedian hypothesis?
Indirect actions of GH

- GH alone does not stimulate cell growth in vitro stimulates secretion of IGFs which do.
- The somatomedins: IGF-1 and -2
- Skeletal actions of IGFs at growth plate
- IGF receptors
- IGF binding proteins
- Laron Dwarfism
- GH
How does growth occur?
Matrix deposition (extracellular)
Protein/DNA ratio
What are the inputs to growth?
Endocrine regulation
General health
Intrauterine growth retardation
Emotional deprivation and psychological factors
How is growth assessed?
Careful history and examination
Consideration of all possible contributors
Use of growth charts
Biochemical and imaging assessment
Describe how history is used in growth assessment.
- Systemic disorders (esp small bowel disease)
- Evidence of skeletal, chromosomal abnormalities
- Endocrine status
- Dietary intake and drugs (glucocorticoids - asthma)
- emotional, psychological, family and school
What is the link between thyroid hormones and growth?
- Thyroid hormones needed for setting metabolic rate
- Also for differentiation
> brain - cretinism occurs in thyroid hormone deficient babies
> skeletal maturation
- Deficiency
> growth retardation. Responds to therapy - catch-up growth
- Permissive actions - needed for GH action.
- Stimulates GH secretion
What is the link between Sex steroids and growth?
- Adrenarche-androgen secretion increases age 6-8, regulated by ACTH. (mainly DHEA)
- Patterns of growth at puberty
> first distal - hands and feet
> then arms and legs
> then trunk
- Testosterone (DHT) actions
> linear, wt growth, muscle mass
> interactions with GH
What is the link between estrogens and growth?
> tissues exquisitively sensitive to E2
> At v. low concentrations, stimulatory
> At high concs, inhibitory
- Androgens and estrogens promote epiphyseal fusion, terminating adolescent growth spurt
- both stimulate GH secretion
What is the link between glucocorticoids and growth?
- Inhibit growth
> all tissues except gonads
> direct action
> protein catabolism (anti-GH), N excretion
- Causes of corticoid excess in children
> adrenal tumour
> cushing's disease
> excess therapy for anti-inflammatory effects
What is the link between Insulin and growth?
- Insulin deficiency in childhood (IDDM)associated with growth retardation
- Growth restored with insulin Rx
- Probably acts via IGF-1 receptor (homologous to insulin receptor)
- Leprechaunism due to insulin receptor defects. Children are born very small and stay below normal size.
What happens with GH Excess and deficiency?
GH excess
- in children causes gigantism
- in adults causes acromegaly

GH deficiency
- in children cause dwarfism
- in adults causes decreased bone density and muscle strength
What can occur with giantism?
Carpal tunnel syndrome.
What are some types of dwarfism?
- Idiopathic GH deficiency
- Laron dwarfism