Normal growth and clinical aspects Flashcards
What factors regulate growth?
Growth hormone release from AP
Thyroid hormones
Insulin
Sex steroids (especially during puberty)
Availability of nutrients
Stress
Genetics
What is growth hormone?
Growth hormone (aka somatotropin) is a peptide hormone released from the Anterior pituitary gland
What secretes growth hormone?
Somatotroph cells of the Anterior pituitary
What controls the level of somatotropin/GH release?
GH release is controlled via the release of two hypothalamic neurohormones with opposing actions:
1) GHIH - aka Somatostatin
2) GHRH
The balance of GHRH : GHIH is determined by the myriad of factors that impinge on the hypothalamus
In what two broad ways does Growth hormone affect our body
Regulates growth and development (indirect action)
Regulates metabolism (direct action)
Summarise the effect of GH on growth and metabolism?
Indirect action
GH necessary for child growth
Even in later life - GH necessary for maintenance and repair of tissue
Describe the role of Growth hormone in growth and development in children
GH is necessary for growth and development of the child.
Growth in the foetal period and the first 8-10 months of life is largely controlled by nutritional intake, but thereafter GH becomes the dominant influence on the rate at which children grow
GH requires permissive action of some other hormones
What are these?
GH requires permissive action of thyroid hormones and insulin before it will stimulate growth
Children with untreated hypothyroidism, or poorly controlled diabetes, have stunted growth despite normal GH levels.
What does Growth hormone stimulate growth at its target tissues?
Growth-promoting effect of GH is mediated through stimulation of both:
cell size (hypertrophy) and
cell division (hyperplasia)
in its many target tissues
Why is the growth-promoting effect of GH indirect?
The effect of GH on growth is achieved through the action of an intermediate known as insulin-like growth factor-I (IGF-1) aka somatomedin C as it mediates the action of GH
Why is IGF-1 described as ‘insulin-like’?
similar to pro-insulin, binds to receptors very similar to the insulin receptor and has hypoglycaemic qualities (hence “insulin-like”)
although latter action is limited to glucose uptake in muscle. Liver and adipose tissue have few IGF receptors
Where is IGF-1 produced?
IGF-I is secreted by the liver, and many other cell types, in response to GH release
and IGF-1 controls GH release through a negative feedback loop
What types of hormones are GH and IGF-1?
How do they travel around in the body?
GH and IGF-I are peptide hormones, but like steroid and thyroid hormones, they are transported in the blood bound to carrier proteins.
~50% of GH is in the bound form - so it acts as a reservoir for smoother release of GH to tissues (as it has a short half life when unbound)
How does IGF-1 provide negative feedback for GH?
Is there any other negative feedback mechanisms?
By inhibiting GHRH and stimulating GHIH
Growth hormone ALSO inhibits Growth hormone release from somatotrophs in AP
What is the effect of GH/IGF-1 on bone growth?
GH stimulates pre-chondrocytes in epiphysial growth plates to differentiate into chondrocytes
During this differentiation, the cells begin to secrete IGF-I and to become responsive to IGF-I
IGF-I then acts as an autocrine or paracrine agent to stimulate the differentiating chondrocytes to undergo cell division and produce cartilage, the foundation for bone growth
What is the effect of growth hormone on metabolism?
Direct effect
- Increases gluconeogenesis in liver
- Reduces sensitivity to Insulin of muscle/adipose tissue cells - less glucose uptake
- Increases sensitivity of adipocytes to lipolytic stimuli
- Increases amino acid uptake and protein synthesis in almost all cells
In the context of metabolism - compare GH to cortisol and insulin
Growth hormone has an anti-insulin effect in muscle/adipose tissue
In this sense - it is similar to Cortisol and different from Insulin
However - GH Increases amino acid uptake and protein synthesis in almost all cells = anabolic effect
(cortisol stimulates protein catabolism).
In this sense - it is similar to Insulin but different from cortisol
What does GH generally do to our metabolism
Stimulates the release of energy stores - to support growth
What is the effect of excess GH on our glucose levels?
GH is diabetogenic (increases blood glucose)
Excess can risk hyperglycaemia
Complete the table showing the effect of Insulin and growth hormones on various things
Summarise the direct effects of Growth hormone on metabolism n shit
In short, Growth hormone:
- Mobilises glucose stores, to increase blood [glucose]
- Inhibits the action of Insulin (by reducing the number of insulin receptors on muscle/adipose tissue) thus augmenting increased blood [glucose]
- Promotes lipolysis - providing alternative source of energy to glucose for most cells of body - augmenting increased blood [glucose]
- Promotes amino acid uptake, thus promoting protein synthesis
During what ages is GH secretion highest?
At what time of day or night?
Highest rate of secretion is during teenage years - although GH found in the pituitaries of both Children and adults
Majority of GH released during first 2 hours of sleep (deep delta sleep)
GH release during waking hours is low
Which hormone’s plasma levels fluctuate more - GH or IGF-1?
[GH] fluctuates a lot - with its peak in first 2 hours of sleep
[IGF-1] is far more stable - suggesting IGF-1 acts as a buffer to GH being wild af
What is the greatest influence over GH secretion?
Nutritional status
as expected given the role of GH in regulating metabolism
Nutritional control of GH release is mainly mediated via changing GHRH/GHIH release from the hypothalamus
What stimulates the release of GHRH?
(and thus stimulates release of GH)
- Current/potential decrease in energy supply to cells
- Increased [amino acids]plasma
- Physical stress & illness
- Delta sleep
- Oestrogen & testosterone
Why does a current state (or potential state) of decreased energy supply to cells stimulate release of GHRH/GH?
As well as growth and development - GH needed for maintenance of tissues and their energy supply
Situations when this happens:
- Hypoglycaemia/fasting causing decreased substrate (energy) supply
- Exercise/cold causing increased demand for energy
Why does increased amounts of amino acids in the plasma stimulate GHRH (& GH) release?
Imagine if you have a big fkn steak
Digestion/absorption of a high protein meal = high [AA] in blood
GH promotes amino acid transport and protein synthesis by muscle and liver - to store all this goodness
If GHRH/GH release is stimulated by physical illness & stress, why does illness generally impede on growth?
Cortisol is also released in response to illness and stress
Cortisol is catabolic so acts against GH in the Growing effect bit
Why do oestrogen and testosterone stimulate the release of GHRH and GH?
They directly stimulate GH release from the pituitary
and
They also decrease IGF-1 mediated negative feedback
This is why we grow a lot in puberty
What are the stimuli that increase GHIH (somatostatin) release and thus decrease GH release
Glucose
FFA
REM sleep
Cortisol
What 3 factors determine growth
Hormones
Nutrition
Genetics
What hormones affect growth?
GH
IGF-I
Thyroid hormones
Sex steroids
Glucocorticoids
Insulin
Using the diagram - explain the relative importances of the Thyroid hormones, growth hormone and Andr/estrogens in growth
Different periods of growth are dominated by different hormones.
Sex hormones influence is minor until puberty when they dominate the growth spurt.
GH influence is also minor during foetal life. Babies born deficient in GH and IGF-1 are of normal size. Insulin and IGF-II may dominate intrauteriene growth
Why are thyroid hormones important to growth?
Thyroid hormones are essential for normal growth
Particularly important for development of the nervous system in utero and early childhood.
Effects are permissive to GH/IGF-I !!!
What is the effect of congenital hypothyroidism?
What causes it to happen?
Retarded growth because of the loss of TH’s permissive action on GH.
GH levels are normal though
Patient will retain infantile facial features.
Reflects maternal iodine deficiency during pregnancy
Deficiencies in both thyroid or growth hormone will massively stunt the growth of a child
What are the differences in growth patterns caused by them?
Hypothyroid - severely stunted growth with infantile proportions still remaining
GH deficiency - severely stunted growth but with normal proportions
Why does disease and injury stunt growth?
Injury and disease both stimulate glucocorticoid release (cortisol)
Cortisol increases protein catabolism
In humans - what are the 2 periods of rapid growth?
Infancy
Puberty
Why does puberty cause a spike in growth?
Puberty means we release androgens and oestrogens - produces spikes in GHRH, GH, IGF-1 = growth
The same sex steroids also terminate growth by causing the epiphyses of the long bones to fuse
How does the effect of GH on our bones change when you compare normal puberty to late puberty?
Normal puberty - before epiphyseal growth plates fuse:
- GH/IGF-I promote bone elongation and increased height, weight and body mass
Late puberty:
- Sex hormones in the later stages of puberty act to close the epiphyses and hence stop bone elongation
What diseases relate to the hypersecretion of GH?
Gigantism:
- excess GH due to a pituitary tumour before epiphyseal plates of long bones close (young age)
- excessive growth, may be more than 7ft tall (210cm), called pituitary giants
Acromegaly:
- excess GH due to a pituitary tumour after epiphyseal plates have sealed.
Describe the growth pattern seen in acromegaly
Long bones cannot increase in length so NO longitudinal growth and NO height increase
However, can still grow in other directions and the characteristic features are enlarged hands and feet
In adults feet should NOT get bigger = classic sign of ACROMEGALY
How is acromegaly/gigantism treated?
Surgery to remove tumour
Somatostatin analogues
What are the main signs of acromegaly?
Normal height but enlarged hands and feet
Hunched back - Osteoarthritic vertebral changes
Bitemporal hemianopia
Prognathism and acromegaly facies
Gynecomastia and lactation
