Normal Growth and Clinical Aspects Flashcards
Where is GH released from, what does it do, and whats another name for it?
Anterior pit. gland
Promotes growth
Somatotrophin
What is somatostatin also called? Whats a good way of remembering this? Where is it released?
GH inhibiting hormone
Statin means stasis
Hypothalamus
Can you use GH of non-human species ?
No - species specific
What does GH need in order to stim growth?
Needs permissive action from thyroid hormones and insulin
What type of hormone is GH, what’s unusual about it?
Peptide
Unusual as even though it is a peptide ~50% still bound to carrier proteins
Functions of GH?
Growth and development
Maintenance of tissues and energy supply
What controls most of growth in foetal period and 1st 8-10 months of life?
Nutritional intake
When does GH become a predominant influence on growth?
After ~10 months
What mediates the growth promoting effect of GH?
Stimulation of cell size and cell division
What is increase in cell size and division known as ?
Hypertrophy and hyperplasia respectively
Is GH’s affect on growth direct or indirect?
Indirect
How does GH affect growth?
Via the action of an intermediate - IGF-1 (Insulin-like growth factor-1)
What is IGF-I also known as?
Somatomedin
How is IGF-1 similar to insulin?
Similar structure to pro-insulin
Binds to receptors similar to insulin receptors
Has hypoglycaemic qualities
Where is IGF-1’s hypoglycaemic qualities focused?
Muscle tissue
What secretes IGF-1 and when is it released?
Liver and many other cell types in response to GH release
What does IGF-1 do?
Controls GH release through a neg. feedback loop
What does IGF-2 do?
Function limited to foetus and neonate
How does IGF-1 create a feedback loop?
Inhibits GHRH and stimulates GHIH/somatostatin
What other feedback loops exist for GH?
GH itself acts as a neg. feedback loop
What does GH/IGF-1 do to bone?
Turns prechondrocytes –> chondrocytes in the epiphyseal plates
During this differentiation the cells secrete IGF-1 and respond well to IGF-1
IGF-1 then stimulates the differentiating chondrocytes to undergo cell division - making cartilage
When do epipheseal plates close and why? What does this mean?
Adolescence
Under influence of sex steroid hormones
No more longitudinal growth (height)
What are some direct effects of GH?
Increases gluconeogenesis
Increases lipolysis
Reduces glucose uptake via insulin
Cortisol would cause protein catabolism BUT GH does the opposite (like insulin does)
What does cortisol do to proteins?
Stimulates protein catabolsim
Why is GH diabetogenic and what does this word mean?
Because it has an anti-insulin effect
It means it increases BG levels
Does insulin or GH increase AA uptake?
Both
Does insulin or GH increase glucose uptake?`
Just insulin
Does insulin or GH increase protein synthesis?
Both do
How is secretion of GH controlled?
Via secretions of GHRH and Somatostatin/GHIH
Is GH present in large or small quantities? More in kids or adults?
Large in BOTH
Is the rate of secretion of GH/GHRH relatively constant or fluctuates?
It undergoes rapid spontaneous fluctuations as well as increasing/decreasing in response to specific stimuli
What is the basal GH in plasma in children and adults?
0-3ng/ml
Is this 0-3ng/ml an accurate number?
No since spikes of secretion occur every 24 hours or so
Meaning in children and puberty it is 5-8ng/ml and in adults it is 2-4 ng/ml
When in children is GH secretion increased by 20x? Why is this?
Deep delta sleep since general energy requirements are low so energy redirected to growth
What needs to be done in order to get a true picture of hormone status?
Repeated measurements over a period of time
GH plasma levels spike…what about IGF-1?
These remain constant suggesting it buffers the pulsatile variance in GH levels
Why is 50% of GH bound in blood even though it is a peptide hormone?
Helps provide a reservoir of GH in the blood which helps smooth out effects if the erratic secretions
What is somatostatin’s secretion pattern like?
Tends to be “tonic” - slow and responsive to need
Stimuli that increase GHRH = GH secretion?
Actual/potential decrease in energy supply to cells
Increased levels of amino acids in plasma
Stressful stimuli
Delta sleep
Oestrogen and androgens
Why does a decrease in energy supply to cells increase GH levels?
GH needed for maintenance of tissues and their energy supply.
In hypoglycaemia there is a reduced substrate supply
In exercise and in the cold there is an increased demand for energy demand for energy.
All stimulate GH.
Why does increase in AA increase GH?
GH promotes AA transport and protein synthesis
Where is protein synthesised?
Muscle and liver
Give examples of stressful stimuli that increase GH levels?
Infections
Psychological stress
Why is an increase in GH during delta sleep useful for adults?
Repair of tissues
What causes increase in somatostain/GHIH?
Glucose
FFAs
REM sleep
Cortisol
What do subjects deprived of REM sleep show high levels of?
GH
Why does cortisol affect GH activity?
It has an inhibitory effect on growth but mainly because it causes catabolism of proteins rather than releasing GHIH
What 3 factors contribute to growth?
Hormones
Nutrition
Genes
What hormones contribute to growth?
GH IGF-1 Insulin Glucocorticoids Thyroid hormone Sex hormones (Androgens and Oestrogens)
When are sex hormones influence on growth dominant?
After puberty
Is GH and IGF-1 a major growth inducing hormone during the foetal stage?
No - mainly insulin and IGF-2
What are thyroid hormones particularly important for?
Development of the NS in utero and early childhood
What are thyroid hormones effects permissive to?
GH/IGF-1
What affects do thyroid hormones have on the body?
Ossification of cartilage
Teeth maturation
Contours of face and proportions of the body
What is cretinism?
A condition where children are hypothyroid from birth leading to retarded growth and infantile facial features
Known as hypothyroid dwarf
Why does hypothyroidism cause retarded growth?
Loss of THs permissive effects on GH
What levels of GH do hypothyroid dwarfs have?
Normal
Do hypothyroid tadpoles eventual mature into frogs?
No chance man
How does nutrition effect growth?
Need sufficient levels of protein and essential vit. and minerals as well as calories, especially in utero and development in childhood
How does injury and disease stunt growth?
It leads to increased protein catabolism
What do genetic factors do in regards to growth?
Helps determine max growth
What are the 2 periods of rapid growth in humans?
Infancy
Puberty
What happens in puberty to cause growth?
(sex hormones) Androgens and oestrogens produce spikes in GH which increases IGF-1 which promotes bone elongation for height and increases weight and mass
What hormones terminate growth and how?
The same androgens and oestrogens that started it - by causing epiphyses of the long bones to fuse
What causes hypersecretion of GH?
Gigantism
Acromegaly
What causes excess GH in gigamtism ?
A pituitary tumour before the epiphyseal plates of long bones close - which is what leads to excessive growth
What causes excess GH in Acromegaly?
Pit. tumour after epiphyseal plates close
In acromegaly, what does excess GH lead to and why not height growth?
Epiphyseal plates are closed so no height increase
But bones grow in other directions = enlarged hands and feet
What is a classic sign of acromegaly?
Feet should not get bigger in acromegaly
Treatment for acromegaly?
Surgical removing of tumour
Somatostatin analogues
Dwarfism may be due to?
GHRH deficiency GH secreting cells are abnormal Defective GH receptors Genetic mutations Precocious puberty Hypothyroid in children
If there is a GHRH def. what can you do?
Administer GHRH and if you see positive results you found the cause
If GH receptors are defective - why is GH conc. increased in body?
Defective GH receptor prevents IGF-1 release and peripheral tissues cannot respond to growth signal
Loss of IGF-1 inhibition feedback loop of GH leads to high levels of GH
Give an example a type of culture with a genetic condition causing them to be short - what do these genes actually cause on a pathological level?
The pygmy people
Genetic mutation that impairs the ability of cells to produce IGF-I in response to GH
Why does precocious puberty lead to stunted growth?
Excess gonadotropin releasing hormone (GnRH) releases sex hormones which fuse long bones early
Why do hypothyroid children retain infantile features with stunted growth?
Due to loss of permissive effects TH has on GH
This limits bone growth, promotes fat storage and can severely impact neurological development
Main difference between hypothyroid kids and kids deficient in GH?
Hypothyroid children retain infantile proportions
Children deficient in GH are proportionally normal, just small in height
