MED2042 WEEK 9 - Hormones and Sex
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- How is GH secretion regulated?
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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.
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- 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?
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- 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.
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- 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.
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- 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?
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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?
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Hypertrophy
Hyperplasia
Matrix deposition (extracellular)
Protein/DNA ratio - What are the inputs to growth?
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Heredity
Nutrition
Endocrine regulation
General health
Intrauterine growth retardation
Emotional deprivation and psychological factors - How is growth assessed?
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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.
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- IUGR
- 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?
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- 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?
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- 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?
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Estrogens:
> 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?
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- 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?
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- 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?
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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?
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- Idiopathic GH deficiency
- Laron dwarfism