L6 Growth Hormones Flashcards
Where are growth hormones produced?
- synthesised within and released from anterior pituitary somatotrophs
- stable population of approximately 50% of pituitary cells
What is the structure of growth hormone?
- 191AAs of single chain polypeptide
How is production of GH being regulated?
- principally by GHRH and somatostatin (aka GH inhibit hormone) with opposing actions on intracellular Ca2+ and cyclic AMP
- -ve feedback is via GH (ie lots of GH present in the periphery) and Insulin-growth-factor 1 (an inhibitory signal). Both increase somatostatin output. IGF1 also acts at the pituitary to reduce effects of GHRH
- GH is released in pulses (5-8/days each lasting 2-3 hours) triggered by pulses of GHRH and fall in somatostatin
What is somatostatin?
- it brings the opposite effect of GHRH. By increasing somatostatin’s output, it reduces GHRH’s output
Other than GHRH, what else can stimulate the release of GH? (2)
- Ghrelin, released from submucosa cells of stomach and can stimulate GH release and stimulate appetite
- GH production from somatotroph is dependent upon an adequate supply of thyroid hormones: hypothyroid children suffer from shunted growth; oestrogen sensitises pituitary to the action of GHRH so stimulates an increase in GH concentrations
How is GH being transported in blood?
- bound to GH binding protein in blood
What factors can influence GH release?
- Age related= rises around puberty and reduces with age
- sleep wake cycle= GH releases during slow wave sleep
- puberty= rises due to gonadal steroids presence
- increases during fasting; hypoglycaemia; after a protein meal; stress and exercise
How do growth hormones achieve their effects?
- have both metabolic and anabolic actions.
1) Anabolic (making more complex structures) actions are mediated largely through the generation of insulin- like growth factor 1
= IGF1 causes growth promotion
2) Metabolic actions tend to synergise with cortisol and antagonises insulin (so give rise to diabetogenic properties of excess GH
GH actions (11)
1) essential for increasing height (through IGF-1) in children and adolescents
2) stimulates limb growth rather than spinal growth (through IGF-1)
3) essential for normal infant growth and the growth spurt at puberty (through IGF-1)
4) not required for growth in utero. Foetuses with no pituitary, grow just fine
5) increases muscle mass through sarcomere hyperplasia and increases protein synthesis
6) increases in organ size
7) promotes gluconeogenesis and reduced hepatic glucose uptake (so can have glucose flowing around for energy conversion
8) promotes lipolysis
9) stimulates immune system
10) reduces fat mass in elderly patients (do not increase strength)
11) no effects of strength or any other indices of fitness
What effects do growth hormones have on your limbs?
- they increase length of your limbs but do NOT impact spinal growth
What are insulin-like growth factors?
- GHRH -> GH -> IGF-1 -> effects
- IGF-1 is produced by the liver and in many other tissues and binds to IGFBP-3 mainly (IGF binding protein-3)
What are the clinical use of GH?
- too much causes gigantism (before puberty where growth is proportional); acromegaly (after puberty where distinct features grow)
- can be a drug of abuse in sports
- used in meat and milk production and has been used in pig and chicken farming
What is the most common cause of acromegaly?
- 15-20% is due to pituitary adenomas
What is the effect caused by acute reduction in GH?
- it enhances insulin sensitivity due to less GH antagonising the insulins
- for long term reduction, GH are associated with the development of insulin resistance
When would patient present as gigantism/ acromegaly? ( given there’s an excess in GH)
- Gigantism would only manifest before the epiphyseal bone fusion
- acromegaly occurs after epiphyseal fusion leading to disproportionate growth
