Causes growth in almost all tissues of the body that can grow by promoting hypertrophy and hyperplasia and differentiation of different cell types
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How does growth hormone circulate around the body?
Bound to the growth hormone binding protein (weakly bound so that there is rapid release to the tissues)
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Which receptors does GH bind to?
GH receptors on target tissues
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Which cells in the anterior pituitary produce GH?
Somatotrophs
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When is GH high?
During sleep, stress, exercise and starvation
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What stimulates GH secretion?
Growth hormone releasing hormone (GHRH) during hypoglycaemia from the hypothalmus
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What inhibits GH secretion?
Hypothalmic peptides eg somatostatin, insulin like growth factor 1 and obeisity
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Which type of nucleus in the hypothalmus is used when GHRH needs to be released?
Arcuate nucleus (AN)
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Which type of nucleus in the hypothalmus is used when somatostatin needs to be released?
Periventricular nucleus (PVN)
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How do you describe GH secretion?
Pulsatile (controlled by pacemaker neurons) and diurnal
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Why is GH release not a true circadian rhythm?
It is not activated over 24hr period and is associated with the onset of sleep
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Is pulsatility important?
Yes
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How is GH secretion controlled by feedback regulation?
GH stimulates PVN to release somatostatin (**) enters the hypophyseal portal blood system. The ** acts on the antierior pituitary somatotrophs and inhibits secretion GH. At the same time, GH inhibits the AN secreting GHRH and inhibits GH secretion
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What type of effect does acute GH levels have?
Metabolic
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What type of effect does long term GH levels have?
Growth promotion
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Describe the metabolic effects of GH.
Increased: amino acid uptake, protein synthesis, gluconeogenesis/glycogenolysis. Decreased: protein catabolism, lipogenesis, glucose uptake and oxidation
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What does GH release as a factor to mediate the actions of GH?
IGF-1 (insulin-like growth factor 1)
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Where is IGF-1 produced?
In the liver and locally in tissues
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Does IGF-1 have a similar structure to insulin?
Yes
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Describe the role of IGF-1?
Plasma IGF-1 is GH dependent, GH binds to IGF binding proteins produced in the liver and it mediates local growth
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What direct effects does GH have?
Anti-insulin diabeogenic effects. In adipose tissue there is a decrease in lipogenesis and fat accumulation. In liver and skeletal muscle there is an increase in gluconeogenesis, glycogenolysis, blood glucose and protein synthesis
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What indirect effects does GH have?
IGF1 mediates local effects in multiple tissues. IGF-1 has mediated endocrine effects on the liver releasing IGF-1 which negatively feedback to AN release of GHRH
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What does IGF-1 feedback to?
Negatively to the AN and anterior pituitary somatotrophs (inhibiting) and positively to the PVN which stimulates ** production which inhibits GH release
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Are GH effects species specific?
Yes as receptors are very specific to each species
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What does having a similar amino acid sequence mean for GH and prolactin?
There is cross reactivity of GH receptors and prolactin receptors
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Describe GH in terms of milk synthesis
It is generally a weak promotor of milk synthesis but in some species it is a strong inducer of lactogenesis
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What effect does GH have on cattle?
It increases milk production but does not enhance growth production (not used in beef cattle)
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What does excess GH cause and how is it caused?
Caused by pituitary tumours (unregulated amounts of GH). In children (before closure of epiphesial grwoth plates) it causes gigantism. In adults (after closure of epiphyseal growth plates) causes acromegaly- no bone growth only soft tissue growth
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Describe acromegaly symptoms
Soft tissue swelling of internal organs, generalised expansion of skull, pronounced lower jaw protrusion and insulin resistance
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What can cause a deficit in GH secretion?
Pituitary malformation/tumour or a GH receptor mutation (not GH sensitive)
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