Normal Growth and Clinical Aspects Flashcards by Zain Aslam

Where is GH released from, what does it do, and whats another name for it?

Anterior pit. gland
Promotes growth
Somatotrophin

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What is somatostatin also called? Whats a good way of remembering this? Where is it released?

GH inhibiting hormone

Statin means stasis

Hypothalamus

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Can you use GH of non-human species ?

No - species specific

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What does GH need in order to stim growth?

Needs permissive action from thyroid hormones and insulin

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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

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Functions of GH?

Growth and development

Maintenance of tissues and energy supply

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What controls most of growth in foetal period and 1st 8-10 months of life?

Nutritional intake

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When does GH become a predominant influence on growth?

After ~10 months

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What mediates the growth promoting effect of GH?

Stimulation of cell size and cell division

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What is increase in cell size and division known as ?

Hypertrophy and hyperplasia respectively

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Is GH’s affect on growth direct or indirect?

Indirect

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How does GH affect growth?

Via the action of an intermediate - IGF-1 (Insulin-like growth factor-1)

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What is IGF-I also known as?

Somatomedin

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How is IGF-1 similar to insulin?

Similar structure to pro-insulin
Binds to receptors similar to insulin receptors
Has hypoglycaemic qualities

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Where is IGF-1’s hypoglycaemic qualities focused?

Muscle tissue

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What secretes IGF-1 and when is it released?

Liver and many other cell types in response to GH release

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What does IGF-1 do?

Controls GH release through a neg. feedback loop

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What does IGF-2 do?

Function limited to foetus and neonate

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How does IGF-1 create a feedback loop?

Inhibits GHRH and stimulates GHIH/somatostatin

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What other feedback loops exist for GH?

GH itself acts as a neg. feedback loop

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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

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When do epipheseal plates close and why? What does this mean?

Adolescence

Under influence of sex steroid hormones

No more longitudinal growth (height)

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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)

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What does cortisol do to proteins?

Stimulates protein catabolsim

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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?

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